acid-phosphatase and Arthritis--Rheumatoid

Bone loss in rheumatoid arthritis (RA) patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin), serum aminoterminal propeptide of type I collagen (PINP), serum carboxyterminal propeptide of type I collagen (ICTP), bone alkaline phosphatase (BAP), osteocalcin (OC), and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX), N-terminal telopeptide of type 1 collagen (I-NTX), pyridinolines (DPD and PYD), and tartrate-resistant acid phosphatase (TRAP). Bone resorption can be seen either in periarticular bone (demineralization and erosion) or in the total skeleton (osteoporosis). Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

Topics: Acid Phosphatase; Amino Acids; Animals; Arthritis, Rheumatoid; Biomarkers; Bone Remodeling; Collagen Type I; Humans; Isoenzymes; Tartrate-Resistant Acid Phosphatase

Patients with rheumatoid arthritis (RA) often have progression of bone destruction owing to chronic inflammation. Treatment for bone destruction is still insufficient in these patients although goal of treatment has become remission since biologics have been used widely. It is shown that collagen cross-linked C-peptide (CTX- I ) and tartrate-resistant acid phosphatase (TRACP) have correlated with bone destruction in patients with RA, in addition, evidence of new biomarker such as hepatocyte growth factor and macrophage inhibitory factor have been accumulated recently. These biomarkers may help evaluation of bone quality clinically.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Collagen Type I; Female; Hepatocyte Growth Factor; Humans; Interleukin-23; Isoenzymes; Macrophage Migration-Inhibitory Factors; Male; Peptides; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Arthritis, Rheumatoid; Biomarkers; Bone Resorption; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Osteogenesis; Osteoporosis; Osteoprotegerin; Peptide Fragments; Peptides; Procollagen; RANK Ligand; Tartrate-Resistant Acid Phosphatase

The association between elevated serum type 5 TRACP activity and metabolic bone diseases has been recognized for many years. However, serum type 5 TRACP exists as two related isoforms: 5a and 5b. Only isoform 5b is osteoclast-derived; the origin and significance of isoform 5a has hardly been explored. We have used simultaneous immunoassays for type-5 TRACP activity and total type-5 TRACP protein in conjunction with non-denaturing gel electrophoresis and column chromatography to investigate the nature and significance of TRACP isoforms 5a and 5b in end-stage renal disease (ESRD) and rheumatoid arthritis (RA). Our studies have shown that TRACP activity and protein are elevated in approximately 50% of sera from ESRD patients, which is caused by osteoclastic isoform 5b. We have also shown that total TRACP protein, but not TRACP activity, is elevated in approximately 30% of sera from RA patients, which is caused by non-osteoclastic isoform 5a. When macrophages or dendritic cells (DC) were cultured in vitro, abundant TRACP 5a was secreted into the culture medium, whereas TRACP 5b was retained intracellularly by both cell types. This implicates macrophages and DC as potential sources of elevated TRACP 5a in RA. Because TRACP isoform expression may be disease-specific, it is important to be able to distinguish TRACP 5a from 5b. There are four criteria by which to do so: (1) TRACP 5a bears sialic acid residues while TRACP 5b does not; (2) the pH optimum for TRACP 5a is 5.2 while that for TRACP 5b is 5.8; (3) the specific activity of TRACP 5a is significantly lower than that of TRACP 5b; and (4) TRACP 5a is as an uncleaved polypeptide, whereas TRACP 5b is a proteolytically nicked disulfide-linked "heterodimer." The differences in biochemical properties and disease-specific expression of TRACP isoforms 5a and 5b suggest that they are regulated differently and perform separate functions in a tissue-specific manner.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Blotting, Western; Dendritic Cells; Epitopes; Humans; Hydrogen-Ion Concentration; Immunoassay; Isoenzymes; Kidney Failure, Chronic; Macrophages; Peptides; Protein Isoforms; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Autoimmunity; Cartilage, Articular; Esterases; Humans; Knee Joint

The levels of six lysosomal enzymes (acid phosphatase, beta-acetylglucosaminidase, cathepsin D, beta-galactosidase, arylsulfatase A, and beta-glucuronidase) and four neutral and alkaline hydrolases (esterase, inorganic phyrophosphatase, alkaline phosphatase, and 5'-nucleotidase) were measured in osteoarthritic, rheumatoid and control synovia. All enzyme levels in diseased synovium except esterase values in osteoarthritis were significantly elevated compared with controls. The mean values of the group of acid hydrolases and the group of neutral and alkaline hydrolases in osteoarthritic synovia were 1.9- and 2.0-fold greater than those of control specimens. In rheumatoid synovia, the values were 4.2- and 4.5 fold greater than control for the same enzymes. Levels in rheumatoid synovia were significantly higher than those in osteoarthritic synovia with the exception of 5'-nucleotidase. Only a limited correlation between the extents of inflammation present in the synovia and the levels of a lysosomal marker enzyme (cathepsin D) was observed. These results demonstrate that whatever the mechanism, increased levels of acid hydrolases as well as certain neutral and alkaline hydrolases are present in osteoarthritic and rheumatoid synovia, and these enzymes are probably contained in the synovial lining cells.

Topics: Acetylglucosaminidase; Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Cathepsins; Cerebroside-Sulfatase; Esterases; Galactosidases; Glucuronidase; Humans; Hydrolases; Nucleotidases; Osteoarthritis; Peroxidases; Polyethylene Glycols; Pyrophosphatases; Synovial Membrane

Topics: Acid Phosphatase; Aneuploidy; Arthritis, Rheumatoid; Cartilage; Cell Division; Cell Survival; Collagen; Culture Media; Culture Techniques; Endotoxins; Humans; Hyaluronic Acid; Hydrocortisone; Lysosomes; Microbial Collagenase; Microscopy, Electron, Scanning; Mitosis; Synovial Membrane

Topics: Acid Phosphatase; Aged; Arthritis, Rheumatoid; Body Temperature; Calcinosis; Female; Humans; Inflammation; Joint Diseases; Kinins; Knee Joint; Lysosomes; Male; Middle Aged; Proteins; Psoriasis; Synovial Fluid

Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy.. Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline.. At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r = 0.332, P = 0.012), and tender joint count (r = 0.408, P = 0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P < 0.05; P < 0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P < 0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P < 0.05).. Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression.

Topics: Acid Phosphatase; Adolescent; Adult; Antibodies, Monoclonal; Arthritis, Rheumatoid; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infliximab; Isoenzymes; Male; Methotrexate; Middle Aged; Osteoclasts; Pilot Projects; Tartrate-Resistant Acid Phosphatase; Young Adult

A study of activity of 4 lysosomal enzymes (LE) (deoxyribonuclease, acid phosphatase, acid cathepcines and beta-galactosidase) in synovial fluid (SF) depending on month of obtaining of the sample was conducted in 112 patients with rheumatoid arthritis (RA). A statistically significant chronobiological difference in this parameter was shown for all investigated enzymes with its increasing in spring and autumn and decreasing in summer and winter. The mean duration of the disease was 9.05 +/- 0.51 years. The dependence of duration of the effect after single intraarticular injection of glucocorticosteroids (methylprednisolone acetate, triamcinolone acetonide, the composition of the latest with cyclophosphamide and dymethylsulfoxide) upon the month of the puncture was investigated in 194 patients with RA. A statistically significant fluctuation (r < 0.05) of remission duration after single injection was shown only for triamcinolone acetonide +/- cyclophosphamide, but the analysis of graphic distribution gives an opportunity to imagine such a chronobiological law for other lysosomal enzymes. The identical distribution of extremes of LE activity and duration of effect after single intraarticular injection of glucocorticosteroids suggests the chronobiological link of these two parameters.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; beta-Galactosidase; Cathepsins; Chronobiology Phenomena; Deoxyribonucleases; Drug Therapy, Combination; Glucocorticoids; Humans; Lysosomes; Middle Aged; Remission Induction; Seasons; Synovial Fluid; Time Factors

Topics: Acid Phosphatase; Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; L-Lactate Dehydrogenase; Male; Propionates; Prostaglandins E; Prostaglandins F; Synovial Fluid

Topics: Acid Phosphatase; Aged; Arthritis, Rheumatoid; Chromosome Aberrations; Clinical Trials as Topic; Female; Humans; Injections, Intra-Articular; Knee; Knee Joint; Male; Middle Aged; Radiation Effects; Synovial Fluid; Synovial Membrane; Yttrium Isotopes

Rheumatoid arthritis (RA) is a systemic autoimmune disease that often leads to joint damage. The mechanisms of bone damage in RA are complex, involving activation of bone-resorbing osteoclasts (OCs) by synoviocytes and Th17 cells. This study was undertaken to investigate whether B cells play a direct role in osteoclastogenesis through the production of RANKL, the essential cytokine for OC development.. RANKL production by total B cells or sorted B cell subpopulations in the peripheral blood and synovial tissue from healthy donors or anti-cyclic citrullinated peptide-positive patients with RA was examined by flow cytometry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. To define direct effects on osteoclastogenesis, B cells were cocultured with CD14+ monocytes, and OCs were enumerated by tartrate-resistant acid phosphatase staining.. Healthy donor peripheral blood B cells were capable of expressing RANKL upon stimulation, with switched memory B cells (CD27+IgD-) having the highest propensity for RANKL production. Notably, switched memory B cells in the peripheral blood from RA patients expressed significantly more RANKL compared to healthy controls. In RA synovial fluid and tissue, memory B cells were enriched and spontaneously expressed RANKL, with some of these cells visualized adjacent to RANK+ OC precursors. Critically, B cells supported OC differentiation in vitro in a RANKL-dependent manner, and the number of OCs was higher in cultures with RA B cells than in those derived from healthy controls.. These findings reveal the critical importance of B cells in bone homeostasis and their likely contribution to joint destruction in RA.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; B-Lymphocytes; Bone Resorption; Case-Control Studies; Cell Differentiation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunohistochemistry; In Vitro Techniques; Isoenzymes; Monocytes; Osteoclasts; RANK Ligand; Real-Time Polymerase Chain Reaction; RNA, Messenger; Synovial Fluid; Synovial Membrane; Tartrate-Resistant Acid Phosphatase

Recently, the traditional Chinese medicine Tripterygium wilfordii Hook f (TwHF) of the Celastraceae family has attracted increasing attention for its potential therapeutic application in patients with rheumatoid arthritis (RA). It is well accepted that TwHF exerts the antirheumatic activity and mainly depends on its potent anti-inflammatory property. To further explore the therapeutic potential of the well-defined TwHF-derived single compound - celastrol in RA, we study the therapeutic efficacy of celastrol on bone erosion in collagen-induced arthritis (CIA) mice and delineate its effects on osteoclast differentiation and functions in RANKL-induced osteoclast precursors RAW264.7 cell line. In CIA mice, daily injection of celastrol (beginning on day 28 after arthritis induction) markedly suppressed arthritis, and reduced bone damage in the joints as demonstrated by histology and bone micro-computed tomography (CT). The effects were accompanied by reductions of osteoclast cells in joints, serum tartrate-resistant acid phosphatase (TRAP) 5b, and expression of osteoclastic genes (Trap, Ctsk, Ctr, Mmp-9) and transcriptional factors (c-Fos, c-Jun and NFATc1). When RAW264.7 cells were treated with RANKL, celastrol inhibited the formation of TRAP+ multinucleated cells and the bone-resorbing activity in dose-dependent manners. Furthermore, celastrol reduced the RANKL-induced expression of osteoclastic genes and transcriptional factors, as well as phosphorylation of NF-kB and mitogen-activated protein kinases (MAPK). These findings show that celastrol could directly inhibit osteoclast formation and function, suggesting a novel therapeutic strategy of celastrol for managing RA, especially in preventing bone destruction.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Bone Resorption; Cell Differentiation; Cell Line; Gene Expression Regulation; Humans; Isoenzymes; Joints; Medicine, Chinese Traditional; Mice; Mice, Inbred Strains; Osteoclasts; Pentacyclic Triterpenes; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Transcriptional Activation; Tripterygium; Triterpenes

Multinucleated giant cells have been noticed in diverse arthritic conditions since their first description in rheumatoid synovium. However, their role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA) still remains broadly unknown. We aimed to study the presence and characteristics of multinucleated giant cells (MGC) both in synovium and in subchondral bone tissues of patients with OA or RA.. Knee synovial and subchondral bone samples were from age-matched patients undergoing total joint replacement for OA or RA, or non-arthritic post mortem (PM) controls. OA synovium was stratified by histological inflammation grade using index tissue sections. Synovitis was assessed by Krenn score. Histological studies employed specific antibodies against macrophage markers or cathepsin K, or TRAP enzymatic assay.. Inflamed OA and RA synovia displayed more multinucleated giant cells than did non-inflamed OA and PM synovia. There was a significant association between MGC numbers and synovitis severity. A TRAP negative/cathepsin K negative Langhans-like subtype was predominant in OA, whereas both Langhans-like and TRAP-positive/cathepsin K-negative foreign-body-like subtypes were most commonly detected in RA. Plasma-like and foam-like subtypes also were observed in OA and RA synovia, and the latter was found surrounding adipocytes. TRAP positive/cathepsin K positive osteoclasts were only identified adjacent to subchondral bone surfaces. TRAP positive osteoclasts were significantly increased in subchondral bone in OA and RA compared to PM controls.. Multinucleated giant cells are associated with synovitis severity, and subchondral osteoclast numbers are increased in OA, as well as in RA. Further research targeting multinucleated giant cells is warranted to elucidate their contributions to the symptoms and joint damage associated with arthritis.

Topics: Acid Phosphatase; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Calcium; Cathepsin K; Cross-Sectional Studies; Diphosphonates; Female; Giant Cells; Giant Cells, Langhans; Glucocorticoids; Humans; Isoenzymes; Knee Joint; Macrophages; Male; Middle Aged; Osteoarthritis; Osteoclasts; Research Design; Single-Blind Method; Synovial Membrane; Tartrate-Resistant Acid Phosphatase; Tibia; Vitamin D

This study determined the effect of type 17 helper T-cell (Th17) cytokines on osteoclastogenesis in rheumatoid arthritis (RA). The expression of IL-17 and receptor activator of NF-κB ligand (RANKL) was determined in synovial tissue, fibroblast-like synoviocytes (FLSs), and synovial fluids of RA patients using immunostaining and enzyme-linked immunosorbent assay. Th17 cytokine-induced RANKL expression was studied in RA FLS by using real-time PCR, luciferase activity assays, and Western blot analysis. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor and Th17 cytokines, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Osteoclastogenesis was also evaluated after monocytes were co-cultured with IL-17-prestimulated FLS. There was significant correlation between RANKL and IL-17 levels in RA synovial fluid. IL-17, IL-21, and IL-22 increased the expression of Rankl mRNA in RA FLS, and the IL-17-induced RANKL expression decreased by the inhibition of Act1, tumor necrosis factor receptor-associated factor 6, NF-κB, and activator protein-1. Th17 cytokines and IL-17-prestimulated FLS induced osteoclastogenesis from monocytes in the absence of exogenous RANKL. The osteoclastic effect was reduced by inhibition of tumor necrosis factor-α. Th17 cytokines have a dual effect on osteoclastogenesis in RA: direct induction of osteoclastogenesis from monocytes and up-regulation of RANKL production in RA FLS. This Th17 cytokine/RANKL axis could be a potential therapeutic target for bone destruction in RA.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Cell Differentiation; Cytokines; Fibroblasts; Humans; Isoenzymes; Macrophage Colony-Stimulating Factor; Monocytes; Osteoclasts; Osteogenesis; RANK Ligand; Signal Transduction; Synovial Fluid; Tartrate-Resistant Acid Phosphatase; Th17 Cells; TNF Receptor-Associated Factor 6; Transcription Factor AP-1; Tumor Necrosis Factor-alpha; Up-Regulation

We aimed to assess osteoclastogenic potential of peripheral blood mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in different forms of arthritis and to correlate it with inflammatory mediators within intra-articular and circulatory compartments.. Paired PBMC and SFMC samples of patients with rheumatoid arthritis (RA; n = 10) and psoriatic arthritis (PsA; n = 10), and PBMC of healthy controls were cultured to assess osteoclastogenic potential by the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor activator of nuclear factor-κΒ (RANK), cFMS, and TRAP). Osteoclastogenesis was correlated with the arthritis-related inflammatory indicators in serum and synovial fluid (SF).. Number of OCs differentiated from PBMC was significantly higher in RA and PsA compared with control, with RA having more OCs compared with PsA. There was no difference in SFMC OC number between arthritic patients, but RANK expression in OCs differentiated from SFMC was higher in PsA compared with RA. SF of PsA patients more potently induced OC differentiation from control CD3(-)CD19(-)CD56(-)CD11b(+)CD115(+) PBMC compared with RA, paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC gene expression of interleukin-18 and Fas-ligand were observed.. Osteoclastogenic potential is systemically enhanced in patients with RA, paralleled by disordered systemic and local expression of proinflammatory mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our study reveals arthritis-specific mediators associated with the form of arthritis, indicating clinical relevance for diagnosis and treatment.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Psoriatic; Arthritis, Rheumatoid; Case-Control Studies; Cell Count; Cell Differentiation; Cells, Cultured; Female; Humans; Inflammation; Isoenzymes; Leukocytes, Mononuclear; Male; Middle Aged; Osteoclasts; Predictive Value of Tests; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptor, Macrophage Colony-Stimulating Factor; Sensitivity and Specificity; Severity of Illness Index; Synovial Fluid; Tartrate-Resistant Acid Phosphatase

To assess whether any form of osteopontin (OPN) is correlated with bone resorption markers or treatment effects in rheumatoid arthritis (RA).. Subjects comprised 119 patients with RA. RA disease activity was evaluated by Disease Activity Score (DAS) 28, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), rheumatoid factor (RF) and matrix metalloproteinase (MMP)-3. OPN levels in plasma and urine were measured by enzyme-linked immunosorbent assay (ELISA). Levels of tartrate-resistant acid phosphatase (TRACP) 5b in serum and C-terminal telopeptide of type 1 collagen (CTX)-1 in urine were measured by ELISA. Patients were divided into responder and nonresponder groups, and OPN levels were compared at baseline and after treatment.. Levels of full-length OPN in plasma (P-fOPN) were significantly correlated with levels of TRACP 5b (r = 0.44, P < 0.001), urine CTX-1 (r = 0.26, P = 0.004) and MMP-3 (r = 0.34, P < 0.001). Levels of TRACP 5b were significantly correlated with age (r = 0.25, P = 0.007), but levels of P-fOPN were not. After treatment, plasma OPN levels were significantly decreased in responders (P = 0.003). Levels of full-length or thrombin-cleaved forms of OPN in urine were not correlated with TRACP 5b or CTX-1.. Our results suggest that plasma OPN may reflect inflammatory bone destruction in RA patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Blood Sedimentation; Bone Resorption; Collagen Type I; Disability Evaluation; Female; Humans; Isoenzymes; Male; Matrix Metalloproteinase 3; Middle Aged; Osteopontin; Peptides; Severity of Illness Index; Tartrate-Resistant Acid Phosphatase; Time Factors; Treatment Outcome

Bone destruction is a critical pathology involved in the functional disability caused by rheumatoid arthritis (RA). Osteoclasts, which are specialized bone-resorbing cells regulated by cytokines such as RANKL, are implicated in bone destruction in RA. The aim of this study was to determine whether interleukin-21 (IL-21), a potent immunomodulatory 4-α-helical bundle type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice with collagen-induced arthritis (CIA).. The expression of IL-21 in synovial tissue was examined using immunohistochemistry. The concentrations of IL-21 in serum and synovial fluid were determined by enzyme-linked immunosorbent assay. The levels of RANKL and osteoclastogenic markers were measured using real-time polymerase chain reaction. CD14+ monocytes from patients with RA or mouse bone marrow cells were cocultured with fibroblast-like synoviocytes (FLS) from patients with RA or CD4+ T cells from mice with CIA in the presence of IL-21 and subsequently stained for tartrate-resistant acid phosphatase activity to determine osteoclast formation.. IL-21 was up-regulated in the synovium, synovial fluid, and serum of patients with RA and in the synovium and serum of mice with CIA. IL-21 induced RANKL expression in mixed joint cells and CD4+ T cells from mice with CIA and in CD4+ T cells and FLS from patients with RA. Moreover, IL-21 enhanced in vitro osteoclastogenesis without the presence of RANKL-providing cells and by inducing RANKL expression in CD4+ T cells and FLS.. Our data suggest that IL-21 promotes osteoclastogenesis in RA. We believe that therapeutic strategies targeting IL-21 might be effective for the treatment of patients with RA, especially in preventing bone destruction.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers; Bone Marrow Cells; CD4-Positive T-Lymphocytes; Cells, Cultured; Coculture Techniques; Fibroblasts; Humans; Interleukins; Lipopolysaccharide Receptors; Male; Mice; Mice, Inbred DBA; Monocytes; Osteoclasts; RANK Ligand; Synovial Membrane

Bone destruction is a common feature of inflammatory arthritis and is mediated by osteoclasts, the only specialized cells to carry out bone resorption. Aberrant expression of receptor activator of nuclear factor kappa β ligand (RANKL), an inducer of osteoclast differentiation has been linked with bone pathology and the synovial fibroblast in rheumatoid arthritis (RA). In this manuscript, we challenge the current concept that an increase in RANKL expression governs osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis. We determined a 10-fold increase of RANKL mRNA and protein in fibroblasts isolated from RA relative to PPA and OA patients. Peripheral blood mononuclear cells (PBMC) from healthy volunteers were cultured in the presence of RA, PPA and OA synovial fibroblast conditioned medium. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), F-actin ring formation and bone resorption assays. The formation of TRAP(+), VNR(+) multinucleated cells, capable of F-actin ring formation and lacunar resorption in synovial fibroblast conditioned medium cultures occured in the presence of osteoprotegerin (OPG) a RANKL antagonist. Osteoclasts did not form in these cultures in the absence of macrophage colony stimulating factor (M-CSF). Our data suggest that the conditioned medium of pure synovial fibroblast cultures contain inflammatory mediators that can induce osteoclast formation in human PBMC independently of RANKL. Moreover inhibition of the TNF or IL-6 pathway was not sufficient to abolish osteoclastogenic signals derived from arthritic synovial fibroblasts. Collectively, our data clearly show that alternate osteoclastogenic pathways exist in inflammatory arthritis and place the synovial fibroblast as a key regulatory cell in bone and joint destruction, which is a hallmark of autoimmune arthritis.

Topics: Acid Phosphatase; Actins; Arthritis, Rheumatoid; Bone Resorption; Cell Differentiation; Cells, Cultured; Chondrocalcinosis; Culture Media, Conditioned; Fibroblasts; Gene Expression Regulation; Humans; Integrin alphaVbeta3; Interleukin-6; Isoenzymes; Leukocytes, Mononuclear; Osteoarthritis; Osteoclasts; Osteoprotegerin; RANK Ligand; Signal Transduction; Synovial Fluid; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

To investigate the effects of bisphosphonates (Bis) (etidronate, alendronate, and risedronate), alone and in combination with statin, on the BMD (bone mineral density) and bone metabolism of rheumatoid arthritis (RA) patients.. Seventy-seven RA patients who had been receiving prednisolone (PSL) and Bis for over 4 years were divided into two groups: Bis and Bis + statin (n = 42 and 35; average age, 66.4 and 65.3 years; average disease duration, 24.9 and 20.8 years; average PSL dose, 2.4 and 2.7 mg, respectively). Serum levels of NTX (N-terminal telopeptide of type I collagen), TRACP-5b (tartrate-resistant acid phosphate-5b), PICP (C-terminal propeptide of type I procollagen), and RANKL (receptor activator of NF-κB ligand) were measured over an 18-month period of treatment and follow-up. The BMD levels of the two groups at the radius, lumbar spine, and femoral neck were compared using DXA (dual-energy x-ray absorptiometry).. A significant increase was only observed in the BMD of the lumbar spine at 18-months, but the BMDs of the radius and femoral neck decreased during the follow-up period in the Bis group. Meanwhile, a significant increase was observed in the BMD of the lumbar spine in the Bis + statin group during administration and the BMDs of the radius and femoral neck stayed at baseline. Among the markers of bone metabolism, serum NTX was up-regulated after 6 months in the Bis + statin group. Serum TRACP-5b was significantly increased during the follow-up period in the Bis + statin group, but only at 18 months in the Bis group. Serum PICP recovered to base line in the Bis + statin group, whereas that in the Bis group did not observably recover during the post-administration follow-up, but rather decreased.. Our findings suggest that both bone resorption and bone formation were inhibited by long-term administration of Bis alone, whereas combination therapy with Bis + statin may be associated with a less marked inhibition of bone metabolism. Cardiovascular disease is highly prevalent in RA patients and some patients are prescribed statins and bisphosphonate. Bis + statin may confer more benefit to the bone metabolism of these patients compared to Bis alone.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Arthritis, Rheumatoid; Bone Density; Collagen Type I; Diphosphonates; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoenzymes; Longitudinal Studies; Male; Middle Aged; Osteoclasts; Osteogenesis; Peptide Fragments; Peptides; Procollagen; Quinolines; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Treatment Outcome

Chronic autoimmune inflammation, which is commonly observed in rheumatoid arthritis (RA), disrupts the delicate balance between bone resorption and formation causing thedestruction of the bone and joints. We undertook this study to verify the effects of natural grape-seed proanthocyanidin extract (GSPE), an antioxidant, on chronic inflammation and bone destruction. GSPE administration ameliorated the arthritic symptoms of collagen-induced arthritis (CIA), which are representative of cartilage and bone destruction. GSPE treatment reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and osteoclast activity and increased differentiation of mature osteoblasts. Receptor activator of NFκB ligand expression in fibroblasts from RA patients was abrogated with GSPE treatment. GSPE blocked human peripheral blood mononuclear cell-derived osteoclastogenesis and acted as an antioxidant. GSPE improved the arthritic manifestations of CIA mice by simultaneously suppressing osteoclast differentiation and promoting osteoblast differentiation. Our results suggest that GSPE may be beneficial for the treatment of inflammation-associated bone destruction.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Base Sequence; Bone and Bones; Bone Resorption; Cell Differentiation; Cells, Cultured; DNA Primers; Grape Seed Extract; Immunohistochemistry; In Vitro Techniques; Isoenzymes; Male; Mice; Mice, Inbred DBA; Osteoblasts; Osteoclasts; Proanthocyanidins; Real-Time Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by chronic inflammation and joint destruction. In this study, we investigated whether dietary supplementation with alpha lipoic acid (ALA) suppresses collagen-induced arthritis (CIA) in mice. Mice were randomly divided into three groups: (1) a control CIA group was fed a normal diet, (2) a CIA group was fed a 0.1% ALA diet (average ALA intake of 160 mg/kg/day), and (3) a CIA group was fed a 0.5% ALA diet (average ALA intake of 800 mg/kg/day). The ALA-fed mice showed a decreased incidence and severity of arthritis compared to the normal diet group. Radiographic findings revealed a dramatic decrease in bone destruction, and histological findings showed extensively suppressed pathological changes in the ALA-fed mice. The ALA-fed mice exhibited inhibited generation of tartrate resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Additionally, ALA-fed mice reduced production of various proinflammatory cytokines and the soluble receptor activator of NF-κB ligand (sRANKL) in the joint tissues and the sera. In conclusion, dietary supplementation with ALA attenuated inflammatory responses and bone destruction in CIA mice.

Topics: Acid Phosphatase; Animals; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Bone Resorption; Cytokines; Dietary Supplements; Isoenzymes; Male; Mice; Mice, Inbred DBA; Osteoclasts; Radiography; RANK Ligand; Severity of Illness Index; Synovitis; Tartrate-Resistant Acid Phosphatase; Thioctic Acid

Formation of osteoclasts and consequent joint destruction are hallmarks of rheumatoid arthritis (RA). Here we show that LIGHT, a member of the tumour necrosis factor (TNF) superfamily, induced the differentiation into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) of CD14(+) monocytes cocultured with nurse-like cells isolated from RA synovium, but not of freshly isolated CD14(+) monocytes. Receptor activator of nuclear factor-kappaB ligand (RANKL) enhanced this LIGHT-induced generation of TRAP-positive MNCs. The MNCs showed the phenotypical and functional characteristics of osteoclasts; they showed the expression of osteoclast markers such as cathepsin K, actin-ring formation, and the ability to resorb bone. Moreover, the MNCs expressed both matrix metalloproteinase 9 (MMP-9) and MMP-12, but the latter was not expressed in osteoclasts induced from CD14(+) monocytes by RANKL. Immunohistochemical analysis showed that the MMP-12-producing MNCs were present in the erosive areas of joints in RA, but not in the affected joints of osteoarthritic patients. These findings suggested that LIGHT might be involved in the progression of inflammatory bone destruction in RA, and that osteoclast progenitors might become competent for LIGHT-mediated osteoclastogenesis via interactions with synoviocyte-like nurse-like cells.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Bone and Bones; Bone Resorption; Cathepsin K; Cell Differentiation; Cells, Cultured; Coculture Techniques; Humans; Isoenzymes; Matrix Metalloproteinase 12; Matrix Metalloproteinase 9; Monocytes; Osteoclasts; RANK Ligand; Synovial Membrane; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor Ligand Superfamily Member 14

The objective of this study is to determine the effects of adrenomedullin (AM) on IL-1- and TNF-alpha-induced rheumatoid synovial fibroblasts (RASFs)-mediated osteoclastogenesis. The formation of osteoclasts in co-cultures of RASFs and peripheral blood mononuclear cells was evaluated by tartrate-resistant acid phosphatase and resorption pit formation assay. The expression of RANKL, OPG, p-ERK, p-p38, and p-JNK was examined by immunoblotting and quantitative reverse transcription-polymerase chain reaction. AM (1-52) inhibits IL-1- and TNF-alpha-induced RASFs-mediated osteoclastogenesis. AM affected IL-1-, TNF-alpha-induced RANKL and OPG expression in RASFs. AM also inhibits IL-1 and TNF-alpha-induced phosphorylation of ERK-1/2, p38 MAPK, and JNK. Inhibitor of AM (AM 22-52) inhibits the effects of AM on the osteoclastogenesis. These results suggest that AM might be involved in the inflammatory cytokines-mediated osteoclastogenesis and thus bone damage, and indicate that it can be a new therapeutic strategy against joint destruction in RA.

Topics: Acid Phosphatase; Adrenomedullin; Arthritis, Rheumatoid; Coculture Techniques; Fibroblasts; Humans; Interleukin-1; Isoenzymes; Leukocytes, Mononuclear; Mitogen-Activated Protein Kinases; Osteoclasts; Osteoprotegerin; RANK Ligand; Recombinant Proteins; RNA, Messenger; Synovial Membrane; Tartrate-Resistant Acid Phosphatase; Time Factors; Tumor Necrosis Factor-alpha

This study was undertaken to determine the effect of toll-like receptor-3 (TLR3) on the regulation of osteoclastogenic activity in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). The expression of receptor activator of nuclear factor kappa B ligand (RANKL) mRNA and protein in RA-FLS after TLR3 activation was determined using RT-PCR, real-time PCR, western blot analysis, and immunohistochemistry. Human monocytes were cocultured with RA-FLS that had been prestimulated by the TLR3 ligand polyriboinosinic-polyribocytidylic acid and then stained for tartrate-resistant acid phosphatase (TRAP) activity. Other markers of osteoclasts were measured using RT-PCR and real-time PCR. The expression of TLR3 and RANKL was much higher in the RA synovium than in the osteoarthritis (OA) synovium. TLR3 activation induced RANKL expression in RA-FLS, but not in OA-FLS or in normal skin fibroblasts. TLR3 activation also induced the production of IL-1beta but had no effect on IL-17 or TNF-alpha production in RA-FLS. Inhibition of IL-1beta reversed the TLR3-induced upregulation of RANKL expression. Coculture of human monocytes with TLR3-activated RA-FLS or TLR3 ligand-stimulated human monocytes increased the expression of TRAP, RANK, cathepsin K, calcitonin receptor, and MMP-9, reflecting the differentiation of monocytes into osteoclasts. Our results suggest that TLR3 promotes osteoclastogenesis in the RA synovium both directly and indirectly. TLR3 stimulates human monocytes directly to promote osteoclast differentiation. TLR3 induces RANKL expression indirectly in RA-FLS, and the expression of RANKL promotes the differentiation of osteoclasts in the RA synovium. Targeting the TLR3 pathway may be a promising approach to preventing inflammatory bone destruction in RA.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Coculture Techniques; Cytokines; Female; Fibroblasts; Humans; Immunohistochemistry; Isoenzymes; Male; Middle Aged; Monocytes; Osteoarthritis; Osteoclasts; Osteogenesis; RANK Ligand; Synovial Fluid; Tartrate-Resistant Acid Phosphatase; Toll-Like Receptor 3; Up-Regulation

To examine whether grape seed proanthocyanidin extract (GSPE) which is known to act as an antioxidant has therapeutic effect on collagen-induced arthritis (CIA) in mice, an animal model of rheumatoid arthritis. Mice were treated with an intraperitoneal injection of GSPE (10, 50, or 100 mg/kg) or saline. Clinical, histological, and biochemical parameters were assessed. The effects of GSPE on osteoclastogenesis were determined by tartrate-resistant acid phosphatase (TRAP) staining of the inflamed joints and bone-marrow cells cultured with the receptor activator of nuclear factor B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Intracellular levels of hydrogen peroxide were determined using carboxy-dichlorodihydrofluorescein diacetate. GSPE treatment significantly attenuated the severity of CIA in a dose-dependent manner and reduced the histology scores for synovial inflammation, cartilage erosion, bone erosion, and the number of TRAP+ osteoclasts. GSPE treatment significantly reduced the numbers of tumor necrosis factor alpha (TNF-alpha)- or interleukin 17 (IL-17)-producing cells in the synovial tissue and the spontaneous production of TNF-alpha and IL-17 by splenocytes compared with those in the control mice. The serum levels of type-II-collagen-specific IgG2a and plasma levels of 8-isoprostane in the GSPE-treated mice were significantly lower than those in the control mice. GSPE dose-dependently suppressed osteoclastogenesis in vitro. GSPE significantly reduced hydrogen peroxide production by anti-CD3-monoclonal-antibody-stimulated CD4+ splenocytes. These results indicate that intraperitoneal injection of GSPE attenuated CIA in mice. GSPE may be useful in the treatment of rheumatoid arthritis.

Topics: Acid Phosphatase; Animals; Ankle Joint; Antibodies; Arthritis, Experimental; Arthritis, Rheumatoid; Cells, Cultured; Collagen Type II; Disease Models, Animal; Grape Seed Extract; Hydrogen Peroxide; Interleukin-17; Isoenzymes; Isoprostanes; Macrophage Colony-Stimulating Factor; Mice; Mice, Inbred DBA; Osteoclasts; Plant Extracts; Proanthocyanidins; RANK Ligand; Spleen; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is a kind of chronic inflammatory autoimmune disease. The degradation of extracellular matrix and cartilage pave way in understanding the molecular mechanisms in RA. Degradation of cartilage is a more complex event involving the local release of metallaoproteases and lysosomal enzymes that mediate inflammation in joints and in the synovial fluid in RA.. In the present study, the efficacy of a Siddha preparation named Kalpaamruthaa (KA) in ameliorating the disease process via markedly reducing the joint destruction was demonstrated in adjuvant induced arthritis rat model. KA consists of Semecarpus anacardium nut milk extract (SA), dried powder of Emblica officinalis fruit and honey.. Both SA and KA were administered at dose of 150 mg/kg b.wt. for 14 days after 14 days of adjuvant injection in rats. The activity of lysosomal enzymes, the level of collagen, glycosaminoglycans (GAGs) and its degradative products were analyzed in control and experimental animals.. The study revealed that KA exhibited a profound reduction (p<0.05) in the activities of lysosomal enzymes and thereby decreasing (p<0.05) the levels of GAGs and its fractions when compared to arthritis rats. The latter was confirmed by Safrannin O staining for GAGs in the interphalangeal joints of control and experimental animals. The effect of KA was found to be improved than SA and this might be due to the combined interactions of phytoconstituents present in KA.

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Arthritis, Rheumatoid; Aspartic Acid Endopeptidases; Blood Proteins; Cathepsin D; Collagen; Disease Models, Animal; Enzyme Activation; Glycosaminoglycans; Glycoside Hydrolases; Hip Joint; Lysosomes; Male; Plant Extracts; Rats; Rats, Wistar

Human serum contains two related isoforms of TRACP: TRACP 5a and TRACP 5b. Serum TRACP 5a protein is increased in about one third of rheumatoid arthritis (RA) sera. This study was undertaken to examine the significance of serum TRACP isoforms 5a and 5b as disease markers of inflammation and bone destruction in RA. One hundred eighteen patients were recruited including 50 with RA (25 with nodules), 26 with osteoarthritis (OA), and 42 with other rheumatic diseases. Twenty-six healthy adults served as controls. Serum TRACP 5a activity, TRACP 5a protein, and TRACP 5b activity were determined by in-house immunoassays. C-reactive protein (CRP) was determined by in-house immunoassay using commercial antibodies and CRP. Other commercial markers included bone-specific alkaline phosphatase (BALP), C-telopeptides of type-I collagen (ICTP), cartilage glycoprotein-39 (YKL-40), and IgM rheumatoid factors (IgM-RF). Mean TRACP 5a protein was significantly elevated only in RA compared with healthy controls and other disease groups. TRACP 5a protein correlated significantly only with IgM-RF in RA. Among RA patients, mean TRACP 5a protein and IgM RF were significantly higher in nodule formers. In contrast, TRACP 5b activity was slightly elevated in RA and correlated with BALP, ICTP, and YKL-40 but not with IgM-RF or CRP. Mean TRACP 5b activity was no different in RA patients with or without nodules. TRACP isoforms could be useful disease markers in RA; TRACP 5a protein may be a measure of systemic inflammatory macrophage burden and disease severity. TRACP 5b activity is a marker for osteoclast number and perhaps local or systemic bone destruction.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Biomarkers; Female; Humans; Immunohistochemistry; Isoenzymes; Male; Middle Aged; Multivariate Analysis; Osteoarthritis; Regression Analysis; Tartrate-Resistant Acid Phosphatase

To examine the role of matrix metalloproteinases(MMP) expressed by the tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and multinucleated cells in articular cartilage damage.. C57BL/6 mice were immunized by injection of chicken type II(CII) collagen to construct the collagen-induced rheumatoid arthritis(CIA) model. The presence of TRAP positive cells in the synovial tissue of CIA mice was examined by enzyme histochemistry and expression of MMP-2,9 was assessed in TRAP positive cells by immunohistochemistry.. Expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) was detected in TRAP positive mononuclear and multinucleated cell. Quantity of TRAP positive cells and the destruction of articular cartilage had a positive correlation (r(s) =0.903, P<0.01). Expression of MMP-2 and MMP-9 in TRAP positive cells was also correlated significantly with the destruction of articular cartilage (r(s) =0.954, P<0.01).. This study suggests that MMP-2 and MMP-9 expression by TRAP positive mononuclear and multinucleated cells are involved in articular cartilage destruction in CIA.

Topics: Acid Phosphatase; Animals; Arthritis, Rheumatoid; Cartilage, Articular; Cell Nucleus; Collagen; Gene Expression Regulation; Immunohistochemistry; Isoenzymes; Knee Joint; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Tartrate-Resistant Acid Phosphatase

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.

Topics: Acid Phosphatase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Body Weight; Cathepsin D; Diclofenac; Edema; Electromagnetic Fields; Foot; Glucuronidase; Hindlimb; Hyperplasia; Hypertrophy; Lysosomes; Male; Mycobacterium tuberculosis; Rats; Rats, Wistar; Synovial Membrane

Serum tartrate-resistant acid phosphatase (TRACP) consists of 2 structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a activity and protein.. Biotinylated anti-TRACP antibodies were used to immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl phosphate as substrate. TRACP 5a protein was measured with an independent peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for linearity of serum dose response, sensitivity and precision. Reference ranges for TRACP 5a were established from serum of 50 healthy males and 50 healthy age-matched females. Serum TRACP 5a activity and protein were determined in 29 cases of rheumatoid arthritis.. Serum matrix interference in both TRACP 5a assays required dilution to 10% serum to approach linearity. Intra-assay and inter-assay CV% were <10%. Mean serum TRACP 5a activity and protein were significantly higher in healthy men than women. There was a slight, but significant age related increase in both serum TRACP 5a and 5b among females, but not males, from age 20 to 70 years. TRACP 5a activity was positively correlated to TRACP 5a protein in healthy sera. Neither TRACP 5a activity nor protein was correlated strongly to TRACP-5b activity. TRACP 5a protein was significantly increased in 8/29 RA sera, whereas TRACP 5a and 5b activities were not. TRACP 5a activity and protein were not significantly correlated in RA sera.. Although TRACP 5a and 5b are related biosynthetically, their circulating levels in healthy humans were independent, suggesting differential regulation of expression. In chronic diseases, increased TRACP 5a may represent pathological processes of inflammation unrelated to bone metabolism.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Immunoassay; Isoenzymes; Male; Middle Aged; Tartrate-Resistant Acid Phosphatase

Our purpose was to develop a specific immunoassay for tartrate-resistant acid phosphatase (TRACP) 5b using naphthol ASBI phosphate (N-ASBI-P) as a selective substrate for isoform 5b and heparin as a selective inhibitor of isoform 5a.. Serum TRACP 5a and 5b and recombinant TRACP 5a were used to optimize and standardize the immunoassay for specificity, linearity, analytical recovery, sensitivity and reproducibility. Serum N-telopeptide cross-links (NTX) and bone alkaline phosphatase (bone ALP) were also measured. The clinical sensitivity and specificity were assessed in healthy control subjects and patients with osteoarthritis (OA), rheumatoid arthritis (RA) and endstage renal disease (ESRD).. TRACP 5b specificity was achieved at pH 6.3 with 2.5 mmol/l substrate and 25 U/ml heparin. Isoform 5b specificity was increased over our original immunoassay using 4-nitrophenyl phosphate (4-NPP) without heparin. The alternative immunoassay was linear with 110% analytical recovery and no serum matrix effects. The average intra-assay error was 10.65%; the average inter-assay error was 10.11% for values of 1-3 U/l and 6.5% for values of 7-11 U/l. Mean serum TRACP 5b in OA and RA were not significantly different from control using either immunoassay. Mean serum TRACP 5b was significantly increased in ESRD with both immunoassays. Serum TRACP 5b levels correlated significantly with NTX and bone ALP in the disease groups, but not always in the control group.. This alternative immunoassay for TRACP 5b activity is highly specific. It should have applications in evaluating patients with bone disease and will improve our understanding of the biological significance of TRACP 5b expression in health and disease.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Chromatography, Ion Exchange; Enzyme Inhibitors; Female; Fluorescent Dyes; Heparin; Humans; Hydrolysis; Immunoassay; Indicators and Reagents; Isoenzymes; Kidney Failure, Chronic; Male; Middle Aged; Neuraminidase; Organophosphorus Compounds; Osteoarthritis; Recombinant Proteins; Tartrate-Resistant Acid Phosphatase; Trypsin

To demonstrate the effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through their effects on receptor activator of nuclear factor kappaB (RANK), osteoprotegerin (OPG), and RANK ligand (RANKL).. Peripheral blood mononuclear cells (PBMCs) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) were cocultured in the presence of macrophage colony-stimulating factor, 1,25-dihydroxyvitamin D(3), and various concentrations of methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), anti-tumor necrosis factor alpha monoclonal antibody (infliximab), interleukin-4 (IL-4), and IL-10. Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase. RANKL expression in RA FLS and RANK expression in PBMCs were assayed by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR. OPG expression was measured by enzyme-linked immunosorbent assay, RT-PCR, and real-time PCR in cultures of RA FLS.. MTX, SSZ, infliximab, and IL-4, but not IL-10 and HCQ, each inhibited osteoclast formation in a dose-dependent manner. We observed no evidence of synergistic inhibition of osteoclast formation by IL-4 and IL-10. High doses of infliximab suppressed the expression of RANK in PBMCs. MTX, SSZ, infliximab, and IL-4 each inhibited the expression of RANKL in RA FLS in a dose-dependent manner, and also increased the secretion of OPG in RA FLS supernatants.. MTX, SSZ, infliximab, and IL-4 inhibit human osteoclastogenesis by modulating the interaction of RANKL, RANK, and OPG. These results are indicative of the underlying mechanisms of the antiresorptive effects of these 4 agents.

Topics: Acid Phosphatase; Antirheumatic Agents; Arthritis, Rheumatoid; Blotting, Western; Carrier Proteins; Cell Survival; Coculture Techniques; Cytokines; Dose-Response Relationship, Drug; Fibroblasts; Glycoproteins; Humans; Isoenzymes; Leukocytes, Mononuclear; Membrane Glycoproteins; Osteoclasts; Osteogenesis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Synovial Membrane; Tartrate-Resistant Acid Phosphatase

To examine the role of tartrate resistant acid phosphatase (TRAP) positive mononuclear and multinucleated cells in the destruction of articular cartilage in patients with rheumatoid arthritis (RA).. The presence of TRAP positive cells in the synovial tissue of patients with RA was examined by enzyme histochemistry and immunohistochemistry. Expression of mRNAs for matrix metalloproteinases (MMPs) was assessed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis. Production of MMPs by mononuclear and multinucleated TRAP positive cells was examined by immunocytochemistry, enzyme linked immunosorbent assay (ELISA) of conditioned medium, and immunohistochemistry of human RA synovial tissue. In addition, a cartilage degradation assay was performed by incubation of (35)S prelabelled cartilage discs with TRAP positive cells.. TRAP positive mononuclear cells and multinucleated cells were found in proliferating synovial tissue adjacent to the bone-cartilage interface in patients with RA. Expression of MMP-2 (gelatinase A), MMP-9 (gelatinase B), MMP-12 (macrophage metalloelastase), and MMP-14 (MT1-MMP) mRNA was detected in TRAP positive mononuclear and multinucleated cells by both RT-PCR and northern blot analysis. Immunocytochemistry for these MMPs showed that MMP-2 and MMP-9 were produced by both TRAP positive mononuclear and multinucleated cells, whereas MMP-12 and MMP-14 were produced by TRAP positive multinucleated cells. MMP-2 and MMP-9 were detected in the conditioned medium of TRAP positive mononuclear cells. TRAP positive mononuclear cells also induced the release of (35)S from prelabelled cartilage discs.. This study suggests that TRAP positive mononuclear and multinucleated cells located in the synovium at the cartilage-synovial interface produce MMP-2 and MMP-9, and may have an important role in articular cartilage destruction in patients with RA.

Topics: Acid Phosphatase; Aged; Animals; Arthritis, Rheumatoid; Blotting, Northern; Cartilage Diseases; Cartilage, Articular; Cattle; Cells, Cultured; Female; Humans; Immunohistochemistry; Isoenzymes; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Middle Aged; Monocytes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Synovial Membrane; Tartrate-Resistant Acid Phosphatase

To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) at sites of joint destruction in rheumatoid arthritis (RA) and to correlate it with the production of matrix metalloproteinases (MMPs).. Reverse transcription-polymerase chain reaction was performed to study the existence of EMMPRIN in synovial tissue derived from RA and osteoarthritis (OA) patients. In situ hybridization with a human complementary DNA specific for EMMPRIN and immunohistochemistry were performed to characterize the EMMPRIN-expressing cells at sites of joint destruction, including bone. Northern blot analysis was performed to detect the level of expression of EMMPRIN messenger RNA (mRNA) in synovial tissue. The production of MMP-1 and MMP-3 by synovial tissue from RA patients was examined by enzyme-linked immunosorbent assay.. Expression of EMMPRIN mRNA was detected in synovium from 9 of 11 patients with RA and 1 of 5 patients with OA. The presence of mRNA encoding EMMPRIN was recognized in the invasive synovium at sites of joint destruction in RA but not OA. Fibroblast-like synovial cells and granulocytes were demonstrated to express EMMPRIN mRNA. MMP-1 and MMP-3 production by synovial tissue was correlated with levels of expression of EMMPRIN mRNA, as detected by Northern blotting.. The expression of EMMPRIN stimulates the production of MMP-1 and MMP-3 in the synovial tissue of affected joints in RA. The results of this study suggest that EMMPRIN may be one of the important factors in progressive joint destruction in RA.

Topics: Acid Phosphatase; Antigens, CD; Antigens, Neoplasm; Arthritis, Rheumatoid; Basigin; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Gene Expression; Humans; In Situ Hybridization; Isoenzymes; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Membrane Glycoproteins; Osteoarthritis; RNA, Messenger; Synovial Membrane; Tartrate-Resistant Acid Phosphatase

Our objective was to evaluate the significance and source of serum tartrate-resistant acid phosphatase (TRACP) in patients with rheumatoid arthritis (RA).. Thirty-five RA, 32 osteoarthritis (OA) and 16 control subjects were studied. Serum TRACP-5b activity and total TRACP protein were determined by immunoassay. TRACP isoforms were analyzed by non-denaturing polyacrylamide gel electrophoresis (PAGE). Serum bone alkaline phosphatase (BAP), cross-linked N-terminal telopeptides (NTx), and C-terminal telopeptides (ICTP) of type I collagen were estimated as markers of bone turnover. C-reactive protein (CRP) was measured as a marker of chronic inflammation. Macrophages and dendritic cells (DC) were developed from peripheral blood monocytes. Cell lysates and culture supernatants were analyzed for TRACP isoforms by immunoassay and PAGE.. In RA, mean TRACP-5b activity was normal, but median total TRACP protein was increased twofold (p<0.001). In OA, TRACP-5b activity and protein were normal. In RA, TRACP-5b activity correlated weakly with ICTP (r=0.56) while TRACP protein levels correlated weakly with NTx (r=0.43). Additionally, TRACP protein, but not TRACP-5b activity correlated significantly with CRP (r=0.42). Macrophage and DC lysates contained TRACP-5b, while tissue culture supernatants contained TRACP-5a.. Increased total TRACP protein in RA sera was probably due to TRACP-5a and not derived from osteoclasts. Rather, it could be a secreted product of inflammatory macrophages and DC.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cells, Cultured; Dendritic Cells; Electrophoresis, Polyacrylamide Gel; Humans; Immunoassay; Inflammation; Isoenzymes; Macrophages; Middle Aged; Osteoarthritis; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (AcP) 5b is a marker of osteoclastic activity and bone resorption. Immunoassays for serum TRAcP may lack sensitivity and specificity because of the presence of non-bone isoform 5a. The purpose of this study was to isolate the serum isoforms, quantify their disease-related expressions, and test an improved immunoassay for TRAcP 5b.. We separated TRAcP isoforms chromatographically from pooled sera of healthy, rheumatoid arthritis (RA) and endstage renal disease (ESRD) subjects. TRAcP isoforms were identified by electrophoresis and quantified by biochemical and immunochemical assays. Serum TRAcP activity in healthy, RA, and ESRD cohorts was assessed at pH 5.5 and 6.1, and compared with bone alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTx).. TRAcP isoforms 5a and 5b were present in all sera; 5b was identical to osteoclastic TRAcP. In serum from healthy subjects, 5a accounted for 87% of the enzyme protein but only 55% of the activity. In RA, both isoforms were increased two- to threefold in protein, but their specific activities were subnormal. In ESRD, only 5b was abnormal, being increased fivefold in protein and threefold in activity. In RA sera, TRAcP activity did not correlate with either BAP or NTx. In ESRD sera, TRAcP activity correlated with BAP and NTx only when measured at pH 6.1.. All sera contained both TRAcP isoforms 5a and 5b, but only 5b was present in bone. TRAcP isoform expression was variable in different diseases. Measurement of TRAcP activity at pH 6.1 improves the specificity of immunoassay for isoform 5b.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Biomarkers; Humans; Immunoassay; Isoenzymes; Kidney Failure, Chronic; Osteoclasts; Reference Values; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (TRAP) isoform 5b is a potential serum marker for osteoclastic activity. Biochemical assays for serum TRAP activity with para-nitrophenylphosphate (pNPP) have low specificity for bone because of hydrolysis by unrelated nontype 5 TRAPs of blood cells and by related isoform 5a. Our purpose was to increase the specificity of TRAP assay for osteoclastic activity by using naphthol-ASBI phosphate (N-ASBI-P) as a substrate for serum type 5 TRAP activity and heparin as an inhibitor of isoform 5a. TRAP activity in individual and pooled sera of normal subjects and patients with endstage renal disease (ESRD) and rheumatologic diseases was quantitated using pNPP and N-ASBI-P as substrate at pH 5.5 and 6.1. For some experiments, heparin (23U/ml) was added as a specific inhibitor of isoform 5a activity. Isoforms 5a and 5b were separated from serum pools by cation exchange chromatography and identified by nondenaturing polyacrylamide gel electrophoresis (PAGE). N-ASBI-P was selectively hydrolyzed by TRAP isoform 5b. TRAP assays with pNPP and N-ASBI-P correlated only in ESRD sera, which contained primarily isoform 5b. The two assays did not correlate in normal or rheumatic sera with significant amounts of 5a. Heparin inhibited isoform 5a activity approximately 50% but had little effect on isoform 5b activity. Biochemical assay of serum TRAP activity can be made specific for isoform 5b by using N-ASBI-P and heparin. This method can be adapted to simple microplate biochemical or immunochemical assays. This simplified method for assessment of osteoclastic TRAP 5b activity warrants a detailed investigation in diseases of bone metabolism.

Topics: Acid Phosphatase; Aniline Compounds; Arthritis, Rheumatoid; Biomarkers; Bone Remodeling; Chromatography, Ion Exchange; Clinical Enzyme Tests; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors; Heparin; Humans; Hydrogen-Ion Concentration; Hydrolysis; Isoenzymes; Kidney Failure, Chronic; Organophosphorus Compounds; Osteoclasts; Osteolysis; Sensitivity and Specificity; Substrate Specificity; Tartrate-Resistant Acid Phosphatase

Bone resorption in the joints is the characteristic finding in patients with rheumatoid arthritis (RA). Osteoclast-like cells are present in the synovial tissues and invade the bone of patients with RA. The characteristics of these cells are not completely known. In the work reported here, we generated these cells from peripheral-blood monocytes from healthy individuals. The monocytes were co-cultured with nurse-like cells from synovial tissues of patients with RA (RA-NLCs). Within 5 weeks of culture, the monocytes were activated and differentiated into mononuclear cells positive for CD14 and tartrate-resistant acid phosphatase (TRAP). These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA. These results indicate that multinucleated giant bone-resorbing cells are generated from monocytes in two steps: first, RA-NLCs induce monocytes to differentiate into TRAP-positive mononuclear cells, which are then induced by cytokines to differentiate into multinucleated giant bone-resorbing cells.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Bone Resorption; Cell Differentiation; Cells, Cultured; Coculture Techniques; Cytokines; Giant Cells; Humans; Isoenzymes; Lipopolysaccharide Receptors; Monocytes; Osteoclasts; Synovial Fluid; Synovial Membrane; Tartrate-Resistant Acid Phosphatase

To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA).. After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrate-resistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor kappaB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe.. TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion.. Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.

Topics: Acid Phosphatase; Animals; Arthritis, Rheumatoid; Biomarkers; Bone Diseases; Carrier Proteins; Collagen; Disease Models, Animal; Female; Histocytochemistry; In Situ Hybridization; Isoenzymes; Membrane Glycoproteins; RANK Ligand; Rats; Receptors, Calcitonin; Tartrate-Resistant Acid Phosphatase

The objective of this study was to identify the isoform, type-5a or type-5b, responsible for increased tartrate-resistant acid phosphatase (TRAP) activity in endstage renal disease (ESRD) and TRAP protein in rheumatoid arthritis (RA). We studied 24 sera each from healthy, ESRD and RA subjects. Type-5 TRAP activity and protein were quantitated by immunoassays. Isoform expression was determined by computerized imaging of non-denaturing polyacrylamide gels (PAGE) stained for TRAP activity. Other biochemical markers included: intact parathyroid hormone (iPTH), total and bone-specific alkaline phosphatase (TAP, BAP), N-telopeptides of type-I collagen (NTx), and free pyridinoline (Pyd). Isoform 5a was normal in both ESRD and RA. Isoform 5b was elevated in ESRD only. Serum TRAP activity correlated with both isoforms 5a and 5b in RA, but only with 5b in ESRD. TRAP protein assays did not correlate with PAGE assays for 5a or 5b. TRAP activity, but not protein, correlated with BAP and NTx in RA sera. Both TRAP activity and protein correlated with iPTH, TAP and Pyd in ESRD sera. Increased TRAP activity in ESRD was due to increased osteoclastic isoform 5b and related to bone turnover. Increased TRAP protein in RA was suspected, but not proven, to be isoform 5a and not related to bone turnover. Heterogeneity of serum TRAP and preferential expression of isoforms has clinical significance in different diseases including ESRD and RA.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Bone and Bones; Electrophoresis, Polyacrylamide Gel; Humans; Isoenzymes; Kidney Failure, Chronic; Tartrate-Resistant Acid Phosphatase

This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04+/-1.98, n = 49, P < .05; female: 1.49+/-2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93+/-1.49, P < .05; female: 1.66+/-2.42, P < .05) compared with normal subjects: but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37+/-2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30-75 years (n = 95) were inversely and significantly correlated with stiffness (r = -.465, P < .01 ), SOS (r = -.484, P < .01), and BUA (r = -.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = -.521, P < .05) and SOS (r = -.527, P < .05) only in the age group of 46-55 years. BUA (r = -.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Bone Remodeling; Case-Control Studies; Colitis, Ulcerative; Female; Fluorides; Humans; Male; Middle Aged; Osteogenesis Imperfecta; Osteoporosis; Predictive Value of Tests; Reference Values; Renal Dialysis; Tartrates; Ultrasonography

Focal resorption of bone at the bone-pannus interface is common in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in significant morbidity. However, the specific cellular and hormonal mechanisms involved in this process are not well established. We examined tissue sections from areas of bone erosion in patients with RA and JRA. Multinucleated cells (MNCs) were present in resorption lacunae in areas of calcified cartilage and in subchondral bone immediately adjacent to calcified cartilage, as previously described. mRNA for the calcitonin receptor (CTR) was localized to these MNCs in bone resorption lacunae, a finding that definitively identifies these cells as osteoclasts. These MNCs were also positive for tartrate-resistant acid phosphatase (TRAP) mRNA and TRAP enzymatic activity. Occasional mononuclear cells on the bone surface were also CTR positive. Mononuclear cells and MNCs not on bone surfaces were CTR negative. The restriction of CTR-positive cells to the surface of mineralized tissues suggests that bone and/or calcified cartilage provide signals that are critical for the differentiation of hematopoietic osteoclast precursors to fully differentiated osteoclasts. Some MNCs and mononuclear cells off bone and within invading tissues were TRAP positive. These cells likely represent the precursors of the CTR-TRAP-positive cells on bone. Parathyroid hormone receptor mRNA was present in cells with the phenotypic appearance of osteoblasts, in close proximity to MNCs, and in occasional cells within pannus tissue, but not in the MNCs in bone resorption lacunae. These findings demonstrate that osteoclasts within the rheumatoid lesion do not express parathyroid hormone receptor. In conclusion, the resorbing cells in RA exhibit a definitive osteoclastic phenotype, suggesting that pharmacological agents that inhibit osteoclast recruitment or activity are rational targets for blocking focal bone erosion in patients with RA and JRA.

Topics: Acid Phosphatase; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Arthritis, Juvenile; Arthritis, Rheumatoid; Biomarkers; Bone Resorption; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes; Macrophages; Osteoclasts; Receptors, Parathyroid Hormone; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH)2vitaminD3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/ macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis.

Topics: Acid Phosphatase; Aged; Arthritis, Rheumatoid; Bone Resorption; Calcitriol; Cell Differentiation; Cells, Cultured; Coculture Techniques; Female; Fibroblasts; Humans; Isoenzymes; Kinetics; Macrophage Colony-Stimulating Factor; Microscopy, Electron, Scanning; Middle Aged; Osteoclasts; Receptors, Calcitonin; Receptors, Vitronectin; Stromal Cells; Synovial Membrane; Tartrate-Resistant Acid Phosphatase; Time Factors

Inflammatory reactions in rheumatoid arthritis (RA) often cause severe joint destruction. However, the mechanism of bone destruction is still a matter of controversy. To determine whether multinuclear cells found in the rheumatoid synovium can resorb bone, isolated synovial cells were assessed for tartrate-resistant acid phosphatase (TRAP) staining and the ability to resorb bone in a dentine resorption assay. TRAP-positive multinuclear cells were found in six out of 10 samples. These six samples showed resorption pit formation on dentine slices. The other four samples did not form resorption pits. The results of this study demonstrate that TRAP-positive multinuclear cells isolated from the rheumatoid synovium form resorption pits on dentine slices. Our results suggest that inflamed synovial cells in rheumatoid joints might participate in bone destruction.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Bone Resorption; Cells, Cultured; Dentin; Humans; Microscopy, Electron, Scanning; Synovial Membrane; Tartrates

Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Animals; Antigens, CD; Arthritis, Rheumatoid; Cells, Cultured; Female; Humans; Interleukin-6; Male; Mice; Middle Aged; Osteoarthritis; Osteoblasts; Osteoclasts; Phenotype; Receptors, Interleukin; Receptors, Interleukin-6; Solubility; Synovial Fluid; Synovial Membrane

The influx of cells into the synovial intima in rheumatoid joints may include osteoclasts and their precursors. The distribution of osteoclast markers--namely, tartrate resistant acid phosphatase activity and the expression of vitronectin receptor (shown with monoclonal antibodies 13C2 and 23C6)--was therefore examined in synovium obtained from patients with rheumatoid (RA) or degenerative (OA) arthritis. Tartrate resistant acid phosphatase positive cells were found in frozen sections of 60% (n = 30) of RA and 69% (n = 29) of OA synovial membranes. Whereas all synovia tested (four RA, four OA) showed diffuse staining of the lining cells with 13C2, 55% (n = 11) of RA and 57% (n = 14) of OA synovial membranes contained isolated cells stained with 23C6 scattered throughout the tissue. In cultures of synovial cells, tartrate resistant acid phosphatase positive, multinuclear, and 23C6 positive cells were found; these cells did not, however, form resorption pits on bone slices. The results show that fully differentiated osteoclasts are uncommon in synovium from patients with either degenerative or inflammatory arthropathies.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Bone Resorption; Cells, Cultured; Humans; Immunochemistry; Integrins; Microscopy, Electron, Scanning; Osteoarthritis; Receptors, Cytoadhesin; Receptors, Vitronectin; Synovial Membrane

Giant cells are commonly present in inflamed synovium, often in close association with the intimal layer. The nature of these multinucleate cells has been reassessed using new cytochemical and immunochemical techniques.. Cryostat sections of non-inflamed, rheumatoid arthritic and osteoarthritic synovia were analysed for the presence of CD68 and non-specific esterase, markers associated with macrophages; activity of uridine diphosphoglucose dehydrogenase, associated with fibroblast-like synoviocytes; and tartrate resistant acid phosphatase and the vitronectin receptor subunit CD51, associated with osteoclasts.. Giant cells were not seen in non-inflamed tissue. In diseased tissue giant cells in the intimal layer fell into two major groups: CD68 negative or dull cells with high uridine diphosphoglucose dehydrogenase (UDPGD) activity suggestive of true synoviocyte polykaryons; and CD68 positive cells with low UDPGD activity suggestive of macrophage polykaryons. The two groups were seen in samples from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), but the former were more prominent in OA and the latter in RA. Most CD68 positive giant cells also showed tartrate resistant acid phosphatase activity and prominent expression of CD51. As such they were histochemically indistinguishable from osteoclasts, but their bone resorbing capacity remains unknown.. Giant cells in arthritic synovium appear to be of two types, one related to true synoviocytes and one to macrophages.

Topics: Acid Phosphatase; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Arthritis, Rheumatoid; Giant Cells; Humans; Immunohistochemistry; Osteoarthritis; Receptors, Cytoadhesin; Receptors, Vitronectin; Rheumatic Diseases; Synovial Membrane; Uridine Diphosphate Glucose Dehydrogenase

To evaluate the prognostic value of some synovial fluid variables in patients with rheumatoid arthritis.. Twenty-nine patients with erosive rheumatoid arthritis and hydropsy in a knee joint were followed for 7.5 years in a prospective study. At the start of the study the knee joints were aspirated and 15 synovial fluid variables were analyzed. The patients were divided into two groups according to whether or not there had been progress of radiologically detected destruction in the knee joints during the follow-up.. Of the synovial fluid variables at the start, only C3 (p = 0.030) and acid phosphatase (p = 0.047) differed significantly between the groups, the former being lower and the latter higher in patients with deterioration of knee joints.. These preliminary results may indicate that low synovial fluid C3 and high acid phosphatase predict poor prognosis in a joint affected by rheumatoid arthritis.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Complement C3; Female; Follow-Up Studies; Humans; Knee Joint; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Synovial Fluid

Two premenopausal women with rheumatoid arthritis of 16 years' duration were enrolled in a one year conditioning exercise program consisting of walking and low impact aerobics. The effect of exercise on the markers of bone formation (serum bone specific alkaline phosphatase and osteocalcin), bone resorption (urinary calcium/creatine and serum tartrate resistant acid phosphatase), and vertebral bone mineral density as determined by dual photon absorptiometry are discussed.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Alkaline Phosphatase; Arthritis, Rheumatoid; Bone and Bones; Bone Density; Bone Remodeling; Calcium; Creatinine; Exercise; Female; Humans; Middle Aged; Osteocalcin

Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor), expression of its mRNA, and possible roles in bone metabolism were studied in murine primary and clonal osteoblast-like cells. Local bone-resorbing factors such as IL-1, TNF alpha, and LPS strongly induced expression of LIF/D-factor mRNA in both clonal MC3T3-E1 cells and primary osteoblast-like cells. Neither parathyroid hormone nor 1 alpha,25-dihydroxyvitamin D3 stimulated expression of LIF/D-factor mRNA. LIF/D-factor per se did not stimulate expression of its own mRNA. Appreciable amounts of LIF/D-factor were detected in synovial fluids from rheumatoid arthritis (RA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIF/D-factor, IL-1, and IL-6 at the concentrations found in synovial fluids from RA patients greatly enhanced bone resorption, though these cytokines did not stimulate bone resorption when separately applied. This suggests that LIF/D-factor produced by osteoblasts is in concert with other bone-resorbing cytokines such as IL-1 and IL-6 involved in the bone resorption seen in the joints of RA patients. LIF/D-factor specifically bound to MC3T3-E1 cells with an apparent dissociation constant of 161 pM and 1,100 binding sites/cell. LIF/D-factor dose-dependently suppressed incorporation of [3H]thymidine into MC3T3-E1 cells. In addition, it potentiated the alkaline phosphatase activity induced by retinoic acid, though LIF/D-factor alone had no effect on enzyme activity. These results suggest that LIF/D-factor is involved in not only osteoclastic bone resorption but also osteoblast differentiation in conjugation with other osteotropic factors.

Topics: Acid Phosphatase; Animals; Arthritis, Rheumatoid; Bone and Bones; Bone Resorption; Cells, Cultured; Dose-Response Relationship, Drug; Female; Growth Inhibitors; Interleukin-1; Interleukin-6; Leukemia Inhibitory Factor; Lipopolysaccharides; Lymphokines; Mice; Mice, Inbred C57BL; Osteoarthritis; Osteoblasts; Pregnancy; RNA, Messenger; Synovial Fluid; Tretinoin; Tumor Necrosis Factor-alpha

The study on the nature of distribution of certain mendelian markers aimed at specifying their role in determination of rheumatoid arthritis disease was carried out, based on the material from the Family Data Bank of the Department of Epidemiology and Genetics of the rheumatic diseases in this institute comprising data on 200 families of patients with definite rheumatoid arthritis (RA). Antigens of HLA-system (the loci A, B, DR), ABO blood groups, Rh, MN and P, phenotypes of acid erythrocyte phosphatase and the types of haptoglobin were studied. Based on the data from this and the previous studies, it is established that the steadiest deviations of the RA patients groups from the general population concerned the frequency of HLA A11, B12, B27 and DR4, blood group P and phenotypes of the acid erythrocyte phosphatase. When using additional controls--a group of healthy mothers of women-probands from the families with the type of marriage "healthy x healthy", and analysing some pair combinations of the HLA system antigens, it was demonstrated that the most clearly their role in formation of the disease display the antigens DR4, and in their absence--DR3, and B12, whereas accumulation of A11 and B27 depended on the presence of other antigens of HLA loci--A and B. Taken together, these data may imply that genetic markers under study serve, when in certain combinations, as "modifiers" of the major gene, or, in a general case, of major genes of multifactorial disease affecting its appearance and clinical manifestations.

Topics: Acid Phosphatase; Alleles; Arthritis, Rheumatoid; Chromosome Mapping; Female; Genetic Markers; Genotype; Haptoglobins; HLA Antigens; Humans; Models, Genetic; Phenotype

Topics: Acid Phosphatase; Amino Acids; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Humans; Hydroxyproline

Alkaline phosphatase (AP), acid phosphatase and myeloperoxidase (MP) activity and the level of cation protein (CP) in blood and synovial fluid (SF) neutrophils were studied and compared in 54 patients with rheumatoid arthritis (RA) and in 22 patients suffering from primary osteoarthrosis deformans (OAD) combined with reactive synovitis. As compared to the patients with OAD, the patients with RA manifested a significant rise of AP, acid phosphatase and MP activity together with a decrease of the level of CP in blood neutrophils. Meanwhile in SF neutrophils from the patients with RA, all the parameters appeared higher than in OAD and were lower that in blood neutrophils in both the groups. As compared to the routine biochemical and cytological tests, the diagnostic information content of the cytochemical parameters of blood neutrophils (AP, acid phosphatase) and SF neutrophils (AP, acid phosphatase, MP) from the patients with RA (against the patients suffering from OAD) was noticeably higher.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Arthritis, Rheumatoid; Blood Proteins; Clinical Enzyme Tests; Diagnosis, Differential; Female; Histocytochemistry; Humans; Male; Middle Aged; Neutrophils; Osteoarthritis; Peroxidase; Synovial Fluid

Altogether 205 children suffering from rheumatoid arthritis were examined for the morphofunctional status of platelets. Appreciable changes in the functional properties of platelets were revealed together with ultrastructural disorders. The correlation was noted between the characteristics under study as was their relationship with the disease activity and pattern.

Topics: Acid Phosphatase; Adolescent; Arthritis, Rheumatoid; Blood Platelets; Child; Female; Humans; Male; Microscopy, Electron; Platelet Adhesiveness; Platelet Aggregation

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Endodeoxyribonucleases; Female; Humans; Osteoarthritis; Synovial Fluid

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Arthritis, Rheumatoid; Catalase; Female; Glucuronidase; Humans; Microscopy, Electron; Middle Aged; Neutrophils; Peroxidase

Frozen sections of pannus tissue taken from the joints of patients with rheumatoid arthritis have been investigated using immunohistological methods to determine the distribution of subsets of macrophage-like cells in this area. A panel of monoclonal antibodies including reagents specific in normal tissue for interdigitating cells (RFD1), macrophages (RFD7), epithelioid cells, (RFD9), monocytes (UCHMI), and osteoclasts (263C), were used. Indirect immunoperoxidase and combination indirect immunofluorescence procedures revealed the phenotypes of macrophage-like cells in four histologically distinct areas of the tissue: the synovial lining layers, the deeper stroma, areas of perivascular infiltration, and the articular cartilage junction where degeneration was occurring. It was discovered that 80% of the lining cells and a majority of macrophage-like cells of the stroma, express the phenotype RFD1+ RFD7+ UCHMI+. Cells with a typical 'dendritic cell' phenotype (RFD1+ RFD7-) were only present in the perivascular infiltrates, while 'classic macrophages' (RFD7+ RFD1-) were the cells accumulating at the cartilage junction. No significant numbers of RFD9+ epithelioid cells were seen. 263C+ osteoclasts were present in small numbers distributed throughout the stroma but did not appear to be involved in areas of cartilage degradation. This cellular distribution in the pannus is compared with previous studies on the rheumatoid synovium proper. It is concluded that a distinct inflammatory reaction occurs in the pannus and that classic activated macrophages are the cells involved in cartilage degradation.

Topics: Acid Phosphatase; Aged; Antibodies, Monoclonal; Arthritis, Rheumatoid; Cartilage, Articular; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Macrophages; Male; Middle Aged; Synovial Membrane

Topics: Acid Phosphatase; Adult; Alleles; Arthritis, Rheumatoid; Carboxylesterase; Carboxylic Ester Hydrolases; Erythrocytes; Gene Frequency; Humans; Moscow; Phenotype; Phosphoglucomutase

Histochemical and ultrastructural studies of bone-cartilage junctions from 21 rheumatoid knee joints have demonstrated the presence of both osteoclasts and chondroclasts. Significant erosions of bone and mineralized cartilage were observed in 15 specimens, and 6 showed localized erosions of unmineralized (hyaline) cartilage. Chondroclasts, defined by their close association with both mineralized and unmineralized cartilage, were morphologically and histochemically similar to osteoclasts. Our observations suggest that these multinucleate cells play a crucial role in subchondral tissue destruction, but that erosion of unmineralized cartilage is primarily the result of synovial pannus tissue.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Arthritis, Rheumatoid; Bone Resorption; Cartilage, Articular; Humans; Knee Joint; Naphthol AS D Esterase; Osteoclasts

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Gout; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Mitochondria; Rheumatic Nodule; Succinate Dehydrogenase; Synovial Fluid; Synovial Membrane; Thiosulfate Sulfurtransferase; Ubiquinone

This paper describes a morphologic, quantitative, cytochemical study of mononuclear non lymphoid cells in knee synovial fluid in osteoarthritis and various arthritides. Morphologic criteria allow to identify among these cells various synoviocytic and monocytic subtypes with in both types, phagocytic subtypes. Quantitative study shows in arthritides an important afflux of monocytes and a hyperexfoliation of synoviocytes. In fluids with intermediate cellularity, Monocytes/Synoviocytes ratio allows the differential cytodiagnosis between osteoarthrosis and arthritis. All monocytic subtypes and especially the phagocytic one are highly significantly increased in arthritides. Synoviocytic subtypes show a lower increase, except the phagocytic one, which is not changed. Giant multinuclear synoviocytes are found in every type of disease and cannot constitute a cytodiagnosis marker. Alcian Blue and hyaluronidase treatment show hyaluronate in a few percentage of Synoviocytes. Cytoenzymologic study shows that synoviocytes and monocytes are positive in all tested hydrolases: beta Glucuronidase, Acid Phosphatase, alpha Naphthyl Acetate Esterase, these activities being always higher in synoviocytes. With peroxidase, synoviocytes are always negative, so this reaction although it marks only a minority of monocytic population can be used as an extra cytologic criterion for discrimination of mononuclear cells in synovial fluid. In these four enzymes there is no significant quantitative difference at cellular level between osteoarthrosis and arthritides. Lysosomal enzymatic activity in both monocytic and synoviocytic cells confirms their heterophagic properties. However synoviocytic heterophagy seems to be a physiological process not or few affected by inflammatory events. On the opposite, monocytic heterophagy and then macrophagic transformation of monocytes appears as a major aspect of intrasynovial inflammatory reaction. If a large majority of exfoliated synoviocytes comes from A type synovial lining cells and if they belong to Mononuclear Phagocyte System, why do they so weakly, or not, participate as phagocytes to inflammatory reaction.

Topics: Acid Phosphatase; Arthritis, Reactive; Arthritis, Rheumatoid; Chondrocalcinosis; Glucuronidase; Gout; Humans; Joint Diseases; Knee Joint; Naphthol AS D Esterase; Peroxidases; Spondylitis, Ankylosing; Synovial Fluid

Macrophage like cells expressing high concentrations of HLA-DR antigen have been identified in situ within the synovium of patients with rheumatoid arthritis. The characteristics of these cells have been determined using immunohistological analysis and combined cytochemical techniques. It was found that the majority (greater than 80%) of these cells were interspersed within the perivascular lymphocytic infiltrates occurring in the synovium. These cells did not stain with antisera against surface immunoglobulin or any Mc Abs to T lymphocyte markers. Further combined staining demonstrated that the HLA-DR + ve cells did stain with an anti-monocyte monoclonal (FMC-17), but could not be stained with a Mc Ab against C3b receptors. The interfacing of cytochemical reactions for acid phosphatase (ACP) and adenosine triphosphatase (ATPase) with immunofluorescence staining for HLA-DR demonstrated that these cells were ACP - ve ATPase + ve. This analysis led to the conclusion that the HLA-DR + ve cells found in abundance in the rheumatoid synovium expressed identical characteristics to the interdigitating cells of the normal lymph node paracortex. The possible significance of the presence of large numbers of such antigen presenting cells in the rheumatoid synovium is discussed.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Arthritis, Rheumatoid; Fluorescent Antibody Technique; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immune Sera; Macrophages; Synovial Membrane

In rheumatoid arthritis, it is well known that lysosomal enzymes such as lysozyme and acid phosphatase have a function of destroying bone and synovial tissue of joints. In order to analyze the localization and the difference of distribution of lysozyme and acid phosphatase on the synovial tissue of rheumatoid arthritis (RA) and non-RA joints, immunohistochemical and histochemical methods were employed. Lysozyme was detected with formalin-fixed, paraffin-embedded materials in 82 cases of synovial tissue (RA 50 cases, non-RA 32 cases) using the unlabelled peroxidase anti-peroxidase (PAP) method following Taylor, et al. Acid phosphatase was detected with the naphthol AS method using frozen sections. In addition, in some cases of RA, alpha 1-antitrypsin and alpha 1-antichymotrypsin were also examined in synovium by the PAP method. For quantitative analysis of lysozyme in synovial fluid, lyso-plate were used on 98 cases (RA 58 cases, non-RA 40 cases). Further, acid phosphatase was quantitated with phenyl phosphoric acid. The results show, histologically, that lysozyme was more predominantly and more specifically located in the synovial cells, especially in the synovial lining cells of RA joints than non-RA joints. Lysozyme was distributed in the cytoplasm of synovial cells in a fine granular or small globoid pattern. On the other hand, no lysozyme was detected on the infiltrated lymphocytes and plasma cells. Infiltration of leukocytes was relatively slight. Acid phosphatase was intensively located in the same portion of RA synovium as that of lysozyme. Electron microscopically, synovial surface cells showed an increase in number, and they contained dominant, well-developed, rough endoplasmic reticulum and electron dense bodies. Fibrillar matrix were present in the cytoplasm and in the extracellular space in an amorphous pattern. Enzyme activity of lysozyme in 58 RA synovial fluid was 113 +/- 101 (mean +/- standard deviation) micrograms/ml and that in 40 non-RA (11 osteoarthritis, 20 autopsy cases, and others) was 35 +/- 31 micrograms/ml. Acid phosphatase activity of 47 RA was 11.97 +/- 10.45 I.U. (International Unit) and that of 38 non-RA was 5.16 +/- 3.77 I.U. A significant difference of lysosomal enzyme activity was thus found in the synovial fluid between RA and non-RA. Clinical laboratory data, namely, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) as an activity of rheumatic disease were evaluated. Correlation rate between ESR and lysoz

Topics: Acid Phosphatase; Adult; Arthritis, Rheumatoid; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Lysosomes; Male; Middle Aged; Synovial Fluid; Synovial Membrane

The efficacy of anti-inflammatory agents is related to their concentration in the peripheral compartments. In rheumatoid arthritis a drug's affinity for synovial tissue and synovial fluid is a decisive factor in treatment. The short-term efficacy of piroxicam was studied, relating the synovial concentration of prostaglandins and acid phosphatase and LDH to piroxicam synovial and plasma levels. After withdrawal of synovial fluid for pre-treatment measurements, 10 patients received 20 to 30 mg of piroxicam/day for eight days. The drug reached an average level of 3.56 +/- 0.9 micrograms/ml in synovial fluid, and 7.73 +/- 1.6 micrograms/ml in plasma. The acid phosphatase decreased from an initial average level of 29 mu/ml to a final average level of 15.999 mu/ml. The LDH showed an initial average level of 725.3 mu/ml and a final average of 471.2 mu/ml (p less than 0.01). The prostaglandin levels were quantified by two methods: indirectly, by measuring the malonilaldehyde concentration in nMol/ml, which showed an average level decrease of 48.75% in 100% of the cases; and directly, by means of thin layer chromatography and biological assay on rats' gastric fundus, against controls. The disappearance of PGE1 and a significant decrease in PGF2 alpha (100%) were observed. We conclude that piroxicam is an effective drug for the short-term treatment of rheumatoid arthritis. It penetrates rheumatoid synovial fluid, reaching 50% plasma concentrations. It has an anti-prostaglandin action, and could stabilize lysosomal membrane.

Topics: Acid Phosphatase; Adult; Alprostadil; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Dinoprost; Humans; L-Lactate Dehydrogenase; Middle Aged; Piroxicam; Prostaglandin Antagonists; Prostaglandins E; Prostaglandins F; Synovial Fluid; Thiazines

A combination of immunochemical staining for HLA-DR antigens and the histochemical demonstration of enzyme activity has been used to identify specific cell populations in the normal and arthritic synovial lining layers. Such combined staining has revealed that the normal synovial lining contains a proportion of HLA-DR + ve cells, all of which show strong lysosomal enzyme activity. This population is greatly expanded in biopsies from patients with osteoarthritis and these positive cells also express strong ATPase activity. In the rheumatoid synovium five distinct cell types can be identified; all of which are HLA-DR + ve but differ in their morphology and pattern of enzyme activity. Of special interest was the discovery that a small but significant proportion of these cells have the characteristics of the interdigitating cells of the lymph node paracortex. The relationship between the emergence of these heterogeneous populations and the immunological basis of this inflammatory response is discussed.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Arthritis, Rheumatoid; Carboxylesterase; Carboxylic Ester Hydrolases; Fluorescent Antibody Technique; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Osteoarthritis; Synovial Membrane

Topics: Acid Phosphatase; alpha-Glucosidases; Arthritis, Rheumatoid; beta-Galactosidase; beta-Glucosidase; Cathepsins; Clinical Enzyme Tests; Female; Humans; Hyaluronoglucosaminidase; Male

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Osteoarthritis; Rheumatic Diseases

Synovial membrane obtained from the patients, in number of twenty one, suffering from the rheumatoid arthritis of classical type, was surveyed from the stand-point of enzyme histochemistry concentrating on lysosomal enzyme. Examined enzymes were leucine aminopeptidase, acid phosphatase and beta-glucuronidase. The activities of respective enzymes were compared with clinical and pathological activities of disease in each cases. It has been known that these lysosomal enzymes indicate high activity not only in chemical analysis of synovial membrane, but also histochemical observation. The origin of these enzymes, however, has not yet been determined as being derived of the synovial tissue or inflammatory cells. In the present investigation, it has been clarified that the enzyme activities were well localized at lining cell layer, but no activation of enzyme in the inflammatory cells in tissue. Therefore, it is suggested that lysosomal enzyme activity may be one of the factors which act on the destructive process in the rheumatoid arthritis.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Female; Glucuronidase; Histocytochemistry; Humans; Leucyl Aminopeptidase; Lysosomes; Male; Middle Aged; Synovial Membrane

Patients with rheumatoid arthritis frequently have an unexplained thrombocytosis which appears to be related to the severity of the disease process. This report shows that rheumatoid platelets have reduced saline soluble protein per 10(9) platelets, less of a lysosomal enzyme, acid phosphatase, and decreased connective tissue activating peptide (CTAP-III) activity. CTAP-III is a potent connective tissue mitogen, and promotes glycolysis and glycosaminoglycan synthesis, characteristics which make it an interesting candidate for a role as a mediator of inflammation.

Topics: Acid Phosphatase; Adult; Age Factors; Arthritis, Rheumatoid; Blood Platelets; Blood Proteins; Female; Humans; Male; Peptides; Sex Factors; Thrombocytosis

It appears that in rheumatoid arthritis and, to a lesser extent, in the other forms of inflammatory rheumatism, the level of zinc in the blood serum is lowered, whereas synovial zinc is increased. In the synovial fluid, there is a very significant correlation between enzyme activity and the concentration of zinc. Practical experiments aimed at demonstrating in vitro the action of zinc on lacticodeshydrogenase, acid phosphatase, lysozyme and beta-glucuronidase did not produce the anticipated results and do not explain the metabolic disorders of zinc seen during inflammatory rheumatisms.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Enzymes; Glucuronidase; Humans; L-Lactate Dehydrogenase; Muramidase; Synovial Fluid; Zinc

Four group systems of serum proteins (Hp, Gc, Km, Gm) and five group systems of erythrocyte enzymes (AP, PGM1, GPT, AK, EsD) were determined in samples of patients with rheumatoid arthritis and in healthy controls. Statistically significant differences were found in Gm system, namely Gm(1) factor was more frequent in rheumatoid patients than in healthy subjects.

Topics: Acid Phosphatase; Adenylate Kinase; Alanine Transaminase; Arthritis, Rheumatoid; Blood Proteins; Erythrocytes; Esterases; Gene Frequency; Humans; Immunoglobulin Allotypes; Phenotype; Phosphoglucomutase

Sera and synovial fluid were investigated in 45 patients with rheumatoid Arthritis and 50 patients with osteoarthritis in inflammatory exacerbation (control group). The following tests were performed: IgG, IgM, IgA determinations, complement components C3, C3, C4, C3-proactivator, ceruloplasmin, electrophoresis, LDH and total acid phosphatase. 1. Serum levels of the ceruloplasmin, alpha 1, alpha 2 and gamma fractions of electrophoresis are significantly higher in patients with rheumatoid arthritis than in patients with osteoarthritis. 2. Synovial fluid: a) There is a significantly higher concentration of IgG, IgM, IgA, C3-proactivator and total acid phosphatase in the synovial fluid of patients with rheumatoid arthritis. b) C4 is significantly lower in patients with rheumatoid arthritis. c) Both groups were also compared with the help of a point system. Every patient received a plus point when the following criteria were seen: IgM greater than 150 mg/100 ml, C3 greater than 50 mg/100 ml, ceruloplasmin greater than 35 mg/100 ml, alpha 1 greater than 0.21 g%, alpha 2 greater than 0.44 g%, beta greater than 0.60 g% and gamma fraction on electrophoresis greater than 0.90 g%. Another point was added if the criteria ceruloplasmin greater than 22 mg/100 ml and C4 less than 17 mg/100 ml were simultaneously seen. With the help of this points system 48 out of the 50 osteoarthritis patients (96%) received zero points, one received 1 point and one 2 points, as opposed to the patients with rheumatoid arthritis where 35 out of 45 (78%) received one or more points. d) The differentation is not improved through additional testing of the rheumatic factors.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Blood; Ceruloplasmin; Complement System Proteins; Humans; Immunoglobulins; L-Lactate Dehydrogenase; Osteoarthritis; Rheumatoid Factor; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Cell Count; Fibrin; Humans; Proteoglycans; Synovial Fluid; Synovial Membrane; Synovitis

After reviewing previous work on the subjects, the authors show that the synovial fluid in subjects with inflammatory rheumatism contained higher levels of lysozyme and of beta-glucuronidase comparable with those of the acid phosphatases and of lacto-dehydrogenase that they were interested in previously.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Glucuronidase; Humans; Knee Joint; L-Lactate Dehydrogenase; Muramidase; Rheumatic Diseases; Synovial Fluid

Cardiac tamponade due to pericarditis occurred in a patient with rheumatoid arthritis. Aspiration afforded us an opportunity to expand the characterization of pericardial fluid. Elevated acid phosphatase levels, decreased whole hemolytic complement and gamma globulin complexes similar to those found in rheumatoid synovial fluid were noted, supporting the concept of a unitary nature of inflammation in rheumatoid disease.

Topics: Acid Phosphatase; Antigen-Antibody Complex; Arthritis, Rheumatoid; Cardiac Tamponade; Complement Fixation Tests; Complement System Proteins; gamma-Globulins; Humans; Immunodiffusion; Immunoglobulin G; Male; Middle Aged; Pericardial Effusion; Rheumatoid Factor; Ultracentrifugation

The synovial sheath obtained in synovectomy in 35 patients with rheumatic- and rheumatic-visceral forms of rheumatoid arthritis was studied histochemically and immunomorphologically. At early stages of exacerbation of the pathological process in the synovial tissue there were revealed predominantly catabolic processes: an increased permeability of vessels; mucoid oedema; fibrinoid changes in the subintimal layer. Further development of the disease was characterized by predominance of anabolic processes with proliferation of synoviocytes, subintimal histiocytes, productive vasculites, massive lymphoid-plasmocytic infiltration, diffuse, or in the form of lymphoid follicles. Using the immunofluorescent technique the authors revealed luminescence of the rheumatoid factor and gamma=globulin in plasmatic cells, extracellularly, and more rarely in macrophages. Pronounced immunological changes in the synovial sheath in the active course of rheumatoid arthritis were accompanied by a high level of metabolic processes and an intensive phagocytic reaction in synoviocytes and subintimal histiocytes. In observations with a low activity of rheumatoid arthritis the synovial tissue was characterized by low levels of enzymes of oxidative metabolism and hydrolysis, emptying of the capillary bed, processes of sclerosis, hyalinosis, amyloidosis.

Topics: Acid Phosphatase; Adenofibroma; Adult; Aged; Alkaline Phosphatase; Arthritis, Rheumatoid; Capillary Permeability; Chronic Disease; Dihydrolipoamide Dehydrogenase; Female; Fluorescent Antibody Technique; gamma-Globulins; Glucosephosphate Dehydrogenase; Glycerolphosphate Dehydrogenase; Glycosaminoglycans; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Plasma Cells; Radiography; Rheumatoid Factor; Synovial Membrane; Synovitis

Synovial cells from patients with rheumatoid arthritis (RA) when grown in vitro in media supplemented with 20% fetal calf serum failed to show any difference in growth rate, life span, uptake of tritiated thymidine or cellular and nuclear characteristics when compared with synovial cells from patients with osteoarthritis or other joint diseases grown similarly in 20% serum enriched medium. There was also no evidence that lymphocytes and/or sera from RA patients were more cytotoxic to autologous synovial cells than sera and/or lymphocytes from OA patients. It is unlikely that antisynovial antibodies or lymphocytes from RA patients act as triggers for synovial damage.

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Autoradiography; Cells, Cultured; Cytoplasm; Cytotoxicity Tests, Immunologic; Fibroblasts; Fluorescent Antibody Technique; Humans; Lymphocytes; Microscopy, Electron; Osteoarthritis; Photomicrography; Synovial Fluid; Thymidine

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Joint Diseases; Male; Middle Aged; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Esterases; Hexosaminidases; Humans; Knee Joint; Synovial Membrane; Synovitis

The authors show that although the enzyme variations are nil or unimportant in the mechanical joint fluids, they are of some importance in the inflammation fluids, particularly in cases of rheumatoid arthritis. Of those studied so far, the variations are most notable in the dehydrogenases and the phosphatases, the variations being highly significant and related to one another and to the sedimentation rate.

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Amylases; Arthritis, Rheumatoid; Aspartate Aminotransferases; Blood Sedimentation; Diagnosis, Differential; Humans; Hydroxybutyrate Dehydrogenase; Isoenzymes; L-Lactate Dehydrogenase; Pancreatic Elastase; Proteins; Synovial Fluid; Uric Acid

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Female; Glycogen; Humans; Lymphocyte Activation; Lymphocytes; Male; Middle Aged

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Cathepsins; Glucuronidase; Humans; Lysosomes

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Fibrinogen; Glycoproteins; Hexoses; Humans; Isoenzymes; L-Lactate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Aspartate Aminotransferases; Creatine Kinase; Female; Humans; Hydroxybutyrate Dehydrogenase; L-Lactate Dehydrogenase; Male; Penicillamine

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Bone Matrix; Cartilage, Articular; Cathepsins; Female; Hexosaminidases; Humans; Leukocyte Count; Lysosomes; Male; Microscopy, Electron; Middle Aged; Synovectomy; Synovial Fluid; Synovial Membrane

Topics: Acid Phosphatase; Aminosalicylic Acids; Arthritis, Rheumatoid; Chondrocalcinosis; Enzymes; Esterases; Exudates and Transudates; Glucuronidase; Histocytochemistry; Humans; Knee Joint; Lymphocyte Activation; Lymphocytes; Monocytes; Naphthalenes; Osteoarthritis; Osteochondritis; Punctures; Rheumatic Diseases; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Complement System Proteins; Female; Humans; Injections, Intra-Articular; Leukocytes; Methylprednisolone; Middle Aged; Rheumatoid Factor; Synovial Fluid

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Esterases; Female; Histocytochemistry; Humans; Isocitrate Dehydrogenase; L-Lactate Dehydrogenase; Lysosomes; Male; Middle Aged; Mitochondria, Muscle; Muscles; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adolescent; Adult; Arthritis, Juvenile; Arthritis, Rheumatoid; Aspartate Aminotransferases; Fructose-Bisphosphate Aldolase; Humans; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Malate Dehydrogenase; Synovial Fluid

Topics: Acid Phosphatase; Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Arthritis, Rheumatoid; Blood Sedimentation; Female; Hemoglobinometry; Histocytochemistry; Humans; Inflammation; Male; Middle Aged; Neutrophils; Nucleotidases; Osteoarthritis; Serum Albumin; Synovial Fluid; Synovial Membrane; Synovitis

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Leukocyte Count; Lymphocytes; Male; Middle Aged; Monocytes; Nucleotidases; Osteoarthritis; Spondylitis, Ankylosing; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Fatty Acids; Fructose-Bisphosphate Aldolase; Humans; Hydrarthrosis; Hydrogen-Ion Concentration; Injections, Intra-Arterial; Knee; L-Lactate Dehydrogenase; Leukocytes; Lymphocytes; Monocytes; Muramidase; Synovial Fluid; Time Factors

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Arthritis, Rheumatoid; Cartilage, Articular; Cell Division; DNA; Female; Hexosaminidases; Humans; Joints; Leukocyte Count; Lymphocytes; Male; Middle Aged; Plasma Cells; Staining and Labeling; Synovial Fluid; Synovial Membrane

Topics: Acid Phosphatase; Arginase; Arthritis, Rheumatoid; Glycoside Hydrolases; Gout; Humans; Joint Diseases; Osteoarthritis; Peptide Hydrolases; Rheumatic Diseases; Synovial Fluid; Transaminases

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Humans; Knee Joint; Leucyl Aminopeptidase; Oxidoreductases; Synovial Membrane

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Arthritis, Rheumatoid; Aspartate Aminotransferases; Glucose; Humans; Hydrarthrosis; Hydrogen-Ion Concentration; Isoenzymes; L-Lactate Dehydrogenase; Osteoarthritis; Proteins; Recurrence; Synovial Fluid

Topics: Acid Phosphatase; Aminopeptidases; Arthritis, Rheumatoid; Blood Sedimentation; Centrifugation; Hemoglobins; Humans; Hydrogen-Ion Concentration; Hydrolysis; Osteoarthritis; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Humans; Joints; Lymphocytes; Lysosomes; Microscopy, Electron; Synovial Membrane

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Cortisone; Female; Glucocorticoids; Hexosaminidases; Humans; Hydrocortisone; Inflammation; Lysosomes; Male; Middle Aged; Prednisolone; Synovial Fluid; Synovial Membrane

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Bursitis; Fructose-Bisphosphate Aldolase; Gout; Humans; Joint Diseases; Osteoarthritis; Phosphoric Monoester Hydrolases; Synovial Fluid; Transaminases

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Betamethasone; Enzyme Activation; Enzymes; Humans; Hydrocortisone; Injections, Intra-Articular; Knee Joint; Synovial Fluid

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Ceruloplasmin; Fructose-Bisphosphate Aldolase; Humans; Phosphorus; Synovial Fluid; Transaminases

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Arthritis, Rheumatoid; Aspartate Aminotransferases; Fructose-Bisphosphate Aldolase; Humans; Synovial Membrane

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Humans; Hydrocortisone; Injections, Intra-Articular; Knee Joint; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; C-Reactive Protein; Diagnosis, Differential; Gout; Histiocytes; Humans; Joint Diseases; Synovial Fluid; Synovitis; Uric Acid; Viscosity

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Collagen Diseases; Humans; Knee Joint; Lupus Erythematosus, Systemic; Middle Aged; Rheumatoid Factor; Synovial Fluid; Synovitis

Topics: Acid Phosphatase; Adult; Arthritis, Infectious; Arthritis, Rheumatoid; Blood Cell Count; Electrophoresis; Humans; Inflammation; Isoenzymes; Leukocyte Count; Lymphocytes; Osteoarthritis; Synovial Fluid; Synovitis

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis; Arthritis, Rheumatoid; Humans; Joint Diseases; Rheumatic Fever; Rickets; Synovial Fluid; Synovitis

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Cartilage, Articular; Cross Reactions; Culture Techniques; Dihydrolipoamide Dehydrogenase; Glycolysis; Histocytochemistry; Humans; Mucoproteins; Newcastle disease virus; Rubella virus; Synovial Membrane

Topics: Absorption; Acid Phosphatase; Arthritis, Rheumatoid; Colloids; Female; Half-Life; Humans; Injections, Intra-Articular; Knee Joint; Lymph Nodes; Male; Muramidase; Radiotherapy Dosage; Resins, Plant; Synovial Fluid; Synovial Membrane; Yttrium Isotopes

Topics: Acid Phosphatase; Arthritis, Infectious; Arthritis, Reactive; Arthritis, Rheumatoid; Complement Fixation Tests; Complement System Proteins; Fluorescent Antibody Technique; Glucuronidase; Gout; Hemolysis; Humans; Proteins; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Bradykinin; Humans; Kinins; Knee Joint; L-Lactate Dehydrogenase; Leukocyte Count; Osteoarthritis; Pain; Proteins; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Cartilage, Articular; Cathepsins; Glucuronidase; Humans; Knee Joint; Sulfatases; Viscosity

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Collagen Diseases; Dermatomyositis; Humans; Lupus Erythematosus, Systemic; Nephritis; Neutrophils; Peroxidases; Prednisolone

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Cathepsins; Glucuronidase; Hexosaminidases; Humans; Lysosomes; Methods; Synovial Fluid

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Arthritis, Rheumatoid; Esterases; Humans; Peroxidases; Synovial Fluid

Topics: Acid Phosphatase; Adolescent; Adult; Arthritis, Rheumatoid; Cell Membrane; Female; Histocytochemistry; Humans; Lupus Erythematosus, Systemic; Lymphocytes; Lysosomes; Male; Middle Aged; Osmotic Fragility

Topics: Acid Phosphatase; Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Aspirin; Cathepsins; Depression, Chemical; Glucuronidase; Gold; Humans; Hydrocortisone; Hydrogen-Ion Concentration; Hydrolases; In Vitro Techniques; Indomethacin; Knee Joint; Liver; Lysosomes; Osteoarthritis; Phenylbutazone; Phosphoric Monoester Hydrolases; Rabbits; Sulfhydryl Compounds; Synovial Fluid

Topics: Acid Phosphatase; Adult; Arthritis, Rheumatoid; Culture Techniques; Female; Humans; Lysosomes; Male; Middle Aged; Osteoarthritis; Proteins; Synovial Membrane

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Humans; Synovial Fluid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Electrophoresis; Humans; Isoenzymes; Synovial Fluid; Synovial Membrane

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Centrifugation; Culture Media; Cytoplasmic Granules; Humans; In Vitro Techniques; Neutrophils; Staining and Labeling; Synovial Fluid

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Histocytochemistry; Humans; Knee Joint; Microscopy, Electron; Osteoarthritis; Synovial Fluid

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Blood Chemical Analysis; Blood Protein Electrophoresis; Chemical Phenomena; Chemistry, Physical; Humans; Hyaluronoglucosaminidase; Latex Fixation Tests; Physical Examination; Rheumatoid Factor; Serum Albumin; Serum Globulins; Synovial Fluid; Ultrasonics; Viscosity

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Blood Cells; Cathepsins; Clinical Enzyme Tests; Glucuronidase; Humans; Immunodiffusion; Inclusion Bodies; Leukocytes; Phagocytosis; Precipitin Tests; Rheumatic Diseases; Rheumatoid Factor; Synovial Fluid

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Cytoplasm; Electrons; Histocytochemistry; Lysosomes; Microscopy; Microscopy, Electron; Mitochondria; Pathology; Synovial Membrane

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Arthritis; Arthritis, Infectious; Arthritis, Rheumatoid; Chemistry Techniques, Analytical; Diagnosis; Geriatrics; Gout; Humans; Knee Injuries; Osteoarthritis; Phosphoric Monoester Hydrolases; Synovial Fluid; Synovitis; Tuberculosis; Tuberculosis, Osteoarticular

Topics: Acid Phosphatase; Arthritis; Arthritis, Rheumatoid; Cartilage; Cytoplasmic Granules; Electrons; Histocytochemistry; Histological Techniques; Humans; Lysosomes; Microscopy; Microscopy, Electron; Synovial Membrane