fibrin and Osteoarthritis

The purpose of this systematic review is to evaluate the effects of adipose derived mesenchymal stem cells (ADSCs) in the treatment of osteoarthritis (OA) in the clinical setting.. A literature search was performed in the MEDLINE, EMBASE, and The Cochrane Library Database up to January 2017 for inclusion and exclusion criteria. Criteria for inclusion were clinical studies demonstrating the effects of ADSCs on OA, and written in English. The following variables were analyzed: donor site, volume of adipose tissue, preparation of ADSCs, clinical outcomes, and complication rate.. Sixteen studies (knee: 14 studies, multiple joints: 1 study, ankle: 1 study) were included in this systematic review. All of the studies prepared ADSCs in the form of the stromal vascular fraction (SVF). Inconsistencies between studies were found with regards to reported clinical variability, donor sites of SVF, and reported clinical outcomes. Nine studies used either platelet-rich plasma (PRP) (7/16) or fibrin (4/16) or both PRP and Fibrin (1/16), as an adjunct at time of SVF injection. All of the studies reported an improvement in clinical outcomes with the use of SVF. Five studies reported a 90% satisfaction rate, and no study reported any complications with liposuction. Five studies reported on complications, with a 5% incidence of swelling and pain.. This systematic review demonstrated that ADSCs are currently used in the form of SVF. While SVF may produce favorable clinical outcomes with minimal risk of side effects on osteoarthritis, the variability in the data and the use of biological adjuvants have confounded the effectiveness of ADSCs. This study will help surgeons understand the limitations in the literature on ADSCs.. Level IV, systematic review of level IV studies.

Topics: Adipose Tissue; Fibrin; Humans; Osteoarthritis; Platelet-Rich Plasma; Stem Cell Transplantation

Hemophilic arthropathy (HA) is characterized by joint damage following recurrent joint bleeds frequently observed in patients affected by the clotting disorder hemophilia. Joint bleeds or hemarthroses trigger inflammation in the synovial tissue, which promotes damage to the articular cartilage. The plasminogen activation system is integral to fibrinolysis, and the urokinase plasminogen activator, or uPA in particular, is strongly upregulated following hemarthroses. uPA is a serine protease that catalyzes the production of plasmin, a broad-spectrum protease that can degrade fibrin as well as proteins of the joint extracellular matrix and cartilage. Both uPA and plasmin are able to proteolytically generate active forms of matrix metalloproteinases (MMPs). The MMPs are a family of >20 proteases that are secreted as inactive proenzymes and are activated extracellularly. MMPs are involved in the degradation of all types of collagen and proteoglycans that constitute the extracellular matrix, which provides structural support to articular cartilage. The MMPs have an established role in joint destruction following rheumatoid arthritis (RA). They degrade cartilage and bone, indirectly promoting angiogenesis. MMPs are also implicated in the pathology of osteoarthritis (OA), characterized by degradation of the cartilage matrix that precipitates joint damage and deformity. HA shares a number of overlapping pathological characteristics with RA and OA. Here we discuss how the plasminogen activation system and MMPs might exacerbate joint damage in HA, lending insight into novel possible therapeutic targets to reduce the comorbidity of hemophilia.

Topics: Arthritis, Rheumatoid; Collagen; Enzyme Precursors; Fibrin; Fibrinolysin; Hemarthrosis; Hemophilia A; Humans; Matrix Metalloproteinases; Osteoarthritis; Peptide Hydrolases; Plasminogen; Proteoglycans; Urokinase-Type Plasminogen Activator

Cartilage damage in inflammatory arthritis is attributed to inflammatory cytokines and pannus infiltration. Activation of the coagulation system is a well known feature of arthritis, especially in rheumatoid arthritis (RA). Here we describe mechanisms by which fibrin directly mediates cartilage degeneration.. Fibrin deposits were stained on cartilage and synovial tissue of RA and osteoarthritis (OA) patients and in murine adjuvant-induced arthritis (AIA) in wild-type or fibrinogen deficient mice. Fibrinogen expression and procoagulant activity in chondrocytes were evaluated using qRT-PCR analysis and turbidimetry. Chondro-synovial adhesion was studied in co-cultures of human RA cartilage and synoviocytes, and in the AIA model. Calcific deposits were stained in human RA and OA cartilage and in vitro in fibrinogen-stimulated chondrocytes.. Fibrin deposits on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA in wild-type mice, whilst fibrinogen deficient mice were protected. Fibrin upregulated Adamts5 and Mmp13 in chondrocytes. Chondro-synovial adhesion only occurred in fibrin-rich cartilage areas and correlated with cartilage damage. In vitro, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-rich areas. Fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization by inducing pro-calcification genes (Anx5, Pit1, Pc1) and the IL-6 cytokine. Similar fibrin-mediated mechanisms were observed in OA models, but to a lesser extent and without pseudo-membranes formation.. In arthritis, fibrin plaques directly impair cartilage integrity via a triad of catabolism, adhesion, and calcification.. None.

Topics: Animals; Arthritis, Rheumatoid; Cartilage; Chondrocytes; Fibrin; Fibrinogen; Humans; Mice; Osteoarthritis; Synovial Membrane

To date no disease-modifying drugs for osteoarthritis (OA) are available, with treatment limited to the use of pain killers and prosthetic replacement. The ADAMTS (A Disintegrin and Metallo Proteinase with Thrombospondin Motifs) enzyme family is thought to be instrumental in the loss of proteoglycans during cartilage degeneration in OA, and their inhibition was shown to reverse osteoarthritic cartilage degeneration. Locked Nucleic Acid (LNA)-modified antisense oligonucleotides (gapmers) released from biomaterial scaffolds for specific and prolonged ADAMTS inhibition in co-delivered and resident chondrocytes, is an attractive therapeutic strategy. Here, a gapmer sequence identified from a gapmer screen showed 90% ADAMTS5 silencing in a monolayer culture of human OA chondrocytes. Incorporation of the gapmer in a fibrin-hyaluronic acid hydrogel exhibited a sustained release profile up to 14 days. Gapmers loaded in hydrogels were able to transfect both co-embedded chondrocytes and chondrocytes in a neighboring gapmer-free hydrogel, as demonstrated by flow cytometry and confocal microscopy. Efficient knockdown of ADAMTS5 was shown up to 14 days in both cell populations, i.e. the gapmer-loaded and gapmer-free hydrogel. This work demonstrates the use applicability of a hydrogel as a platform for combined local delivery of chondrocytes and an ADAMTS-targeting gapmer for catabolic gene modulation in OA.

Topics: ADAMTS5 Protein; Cells, Cultured; Chondrocytes; Fibrin; Gene Knockdown Techniques; Humans; Hyaluronic Acid; Hydrogels; Oligonucleotides, Antisense; Osteoarthritis

A cell therapy product of transforming growth factor (TGF)-β1-transduced chondrocytes has been commercialized to treat osteoarthritis of the knee via intra-articular injection. The need for arthroscopic application of the cells to simultaneously treat intra-articular pathologies of knee osteoarthritis is increasingly urgent. The purpose of this study was to optimize TGF-β1-transduced chondrocytes for arthroscopic application. The optimal composition of chondrocytes and thrombin was initially determined by measuring the consolidation time of a diverse ratio of chondrocytes and thrombin mixed with 1 ml of fibrinogen. The consolidation time of the diverse ratio of fibrinogen and atelocollagen mixed with the determined optimal ratio of chondrocytes and thrombin was evaluated. The mixture of the determined optimal ratio of TGF-β1-transduced chondrocytes, atelocollagen, fibrinogen, and thrombin was applied to the cartilage defect of the 3D printed knee joint model arthroscopically. The status of the mixture in the defect was then evaluated. Chondrogenic activities of TGF-β1-transduced chondrocytes mixed with atelocollagen were evaluated. The determined ratio of TGF-β1-transduced chondrocytes to thrombin was 8:2 and that of fibrin to atelocollagen was also 8:2. Excellent maintenance of conformation of the mixture of TGF-β1-transduced chondrocytes, atelocollagen, fibrinogen, and thrombin in the cartilage defect of the 3D printed knee joint model was observed arthroscopically. Increased chondrogenic activities were observed in the group of TGF-β1-transduced chondrocytes mixed with atelocollagen. TGF-β1-transduced chondrocytes can be applied arthroscopically to treat cartilage defects of the knee at an optimized mixing ratio of atelocollagen, fibrinogen, and thrombin.

Topics: Arthroscopy; Cartilage; Cell- and Tissue-Based Therapy; Chondrocytes; Collagen; Fibrin; Fibrinogen; Humans; Injections, Intra-Articular; Knee Joint; Osteoarthritis; Printing, Three-Dimensional; Regeneration; Thrombin; Transforming Growth Factor beta1

The aim of this study was to test the hypotheses that retroviral gene transfer of SOX trio enhances the in vitro chondrogenic differentiation of ASCs, and that SOX trio-co-transduced ASCs in fibrin gel promote the healing of osteochondral defects, and arrest the progression of surgically-induced osteoarthritis in a rat model. ASCs isolated from inguinal fat in rats were transduced with SOX trio genes using retrovirus, and further cultured in vitro in pellets for 21 days, then analyzed for gene and protein expression of SOX trio and chondrogenic markers. SOX trio-co-transduced ASCs in fibrin gel were implanted on the osteochondral defect created in the patellar groove of the distal femur, and also injected into the knee joints of rats with surgically-induced osteoarthritis. Rats were sacrificed after 8 weeks, and analyzed grossly and microscopically. After 21 days, ASCs transduced with SOX-5, -6, or -9 had hundreds-fold greater gene expression of each gene compared with the control with the SOX protein expression matching gene expression. SOX trio-co-transduction significantly increased GAG contents as well as type II collagen gene and protein expression. ASCs co-transduced with SOX trio significantly promoted the in vivo cartilage healing in osteochondral defect model, and prevented the progression of degenerative changes in surgically-induced osteoarthritis.

Topics: Adipocytes; Animals; Cartilage, Articular; Cell Differentiation; Cells, Cultured; Disease Progression; Fibrin; Gels; Male; Osteoarthritis; Rats; Rats, Sprague-Dawley; Regeneration; SOX Transcription Factors; SOX9 Transcription Factor; SOXD Transcription Factors; Stem Cells; Transduction, Genetic

The goal of this study was to assess the incorporation of exudates of human platelet-rich fibrin (hPRF) that is abundant in platelet cytokines and growth factors into biodegradable fibrin (FB) scaffolds as a regeneration matrix for promoting chondrocyte proliferation and re-differentiation. hPRF was obtained from human blood by centrifugation without an anticoagulant, and the exudate of hPRF was collected and mixed with bovine fibrinogen, and then thrombin was added to form the FB scaffold. Proliferation and differentiation of human primary chondrocytes and a human chondrosarcoma cell line, the SW-1353, embedded in the three-dimensional (3D) scaffolds and on the two-dimensional (2D) surface of the FB scaffolds so produced were evaluated in comparison with an agarose (AG) scaffold serving as the control. Results demonstrated that the amounts of these cytokines and growth factors in hPRF exudates were higher than those in the blood-derived products except for TGF-β1. Chondrocytes and SW1353 cells on the 2D and 3D FB scaffolds with the addition of the exudates of PRF exhibited more-available proliferation and differentiation than cells on 2D and 3D FB and AG scaffolds. It was concluded that FB scaffolds can provide an appropriate environment for chondrocyte proliferation and re-differentiation, and it could be improved by adding exudates of hPRF. These 3D scaffolds have great promise for cartilage tissue engineering.

Topics: Animals; Biocompatible Materials; Blood Platelets; Cartilage; Cattle; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Chondrocytes; Collagen; Enzyme-Linked Immunosorbent Assay; Exudates and Transudates; Fibrin; Humans; Intercellular Signaling Peptides and Proteins; Osteoarthritis; Sepharose; Tissue Engineering

Peptidylarginine deiminases (PADIs) convert peptidylarginine into citrulline via post-translational modification. Anti-citrullinated peptide antibodies are highly specific for rheumatoid arthritis (RA). Our genome-wide case-control study of single-nucleotide polymorphisms found that the PADI4 gene polymorphism is closely associated with RA. Here, we localized the expression of PADI4 and the citrullinated protein product in synovial RA tissue.. We used immunohistochemistry, double immunofluorescent labelling and western blotting.. We found that PADI4 is extensively expressed in T cells, B cells, macrophages, neutrophils, fibroblast-like cells and endothelial cells in the lining and sublining areas of the RA synovium. We also found extracellular and intracellular expression of PADI4 in fibrin deposits with loose tissue structures where apoptosis was widespread. Unlike PADI4, citrullinated protein generally appeared in fibrin deposits that were abundant in the RA synovium. The citrullinated fibrin aggregate was immunoreactive against immunoglobulin (Ig) A and IgM, but not IgG and IgE. Although a little PADI4 was expressed in osteoarthritic and normal synovial tissues, significant citrullination was undetectable.. The results showed that PADI4 is mainly distributed in cells of various haematopoietic lineages and expressed at high levels in the inflamed RA synovium. The co-localization of PADI4, citrullinated protein and apoptotic cells in fibrin deposits suggests that PADI4 is responsible for fibrin citrullination and is involved in apoptosis. The immunoreactivity of citrullinated fibrin with IgA and IgM in the RA synovium supports the notion that citrullinated fibrin is a potential antigen of RA autoimmunity.

Topics: Apoptosis; Arthritis, Rheumatoid; Blotting, Western; Citrulline; Fibrin; Humans; Hydrolases; Immunophenotyping; Leukocytes; Osteoarthritis; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Synovial Membrane

Clinical and experimental evidence suggests that extravascular fibrin deposition in arthritic joints is prominent and deleterious. The aim of this study was to investigate the contributions of tissue factor (TF) and its inhibitor, TF pathway inhibitor (TFPI), in arthritis.. Synovial tissue specimens obtained from 10 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) were scored histologically for inflammation and fibrin content. TF and TFPI levels were assayed at antigenic and functional levels. TF messenger RNA (mRNA) levels were determined using RNase protection assays. The effect of TF inhibition in murine antigen-induced arthritis (AIA) was assessed by administering systemically active site-blocked activated factor VIIa (FVIIai).. Functional TF activity was significantly increased in synovial membranes from RA patients compared with those from OA patients. In contrast, no difference in TF mRNA and TF antigenic levels was observed between these 2 groups. This discrepancy can be accounted for by TFPI, because we observed a negative correlation between TF activity and TFPI activity. There was a significant difference between the RA and OA groups in terms of synovial inflammation, with more inflammation observed in the RA group. Most importantly, TF activity was associated with fibrin (P = 0.024) and with histologic inflammation (P = 0.03) scores. In AIA, inhibition of TF-induced coagulation by FVIIai led, on day 9 of arthritis, to decreased synovial thickness and decreased articular cartilage damage, although only the latter difference between controls and treated mice reached significance (P < 0.04). Finally, in FVIIai-treated mice, there was a strong negative association between the prothrombin time and intraarticular fibrin deposition.. Our results show that TF expression in arthritic synovial tissue favors extravascular coagulation and may play a role in inflammation in RA. In this context, TF inhibitors may be of therapeutic value.

Topics: Aged; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Dansyl Compounds; Disease Models, Animal; Factor VIIa; Female; Fibrin; Fibrinolytic Agents; Hindlimb; Humans; Immunohistochemistry; Lipoproteins; Male; Mice; Mice, Inbred C57BL; Middle Aged; Osteoarthritis; Radionuclide Imaging; RNA, Messenger; Synovitis; Thromboplastin

Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis.. To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint.. Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences.. Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT.. Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.

Topics: Adult; Aged; Arthritis; Arthritis, Rheumatoid; Biomarkers; Blood Coagulation; Carboxypeptidase B2; Case-Control Studies; Female; Fibrin; Fibrinolysis; Humans; Inflammation; Linear Models; Male; Middle Aged; Osteoarthritis; Spondylitis, Ankylosing; Synovial Fluid

We evaluated histologically samples of synovial tissue from the knees of 50 patients with rheumatoid arthritis (RA). The samples were taken during revision for aseptic loosening. The findings were compared with those in 64 knees with osteoarthritis (OA) and aseptic loosening and in 18 knees with RA without loosening. The last group had been revised because of failure of the inlay or the coupling system of a constrained prosthesis. All the patients had had a total ventral synovectomy before implantation of the primary prosthesis. In all three groups a foreign-body reaction and lymphocellular infiltration were seen in more than 80% of the tissue samples. Deposits of fibrin were observed in about one-third to one-half of the knees in all groups. Typical signs of the reactivation of RA such as rheumatoid necrosis and/or proliferation of synovial stromal cells were found in 26% of knees with RA and loosening, but not in those with OA and loosening and in those with RA without loosening. Our findings show that reactivation of rheumatoid synovitis occurs after total knee replacement and may be a cofactor in aseptic loosening in patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Female; Fibrin; Foreign-Body Reaction; Humans; Knee Prosthesis; Lymphocytes; Male; Middle Aged; Osteoarthritis; Prosthesis Failure; Recurrence; Reoperation; Synovitis

Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.

Topics: Animals; Antigens; Apolipoproteins A; Arthritis; Arthritis, Rheumatoid; Fibrin; Humans; Joints; Lipoprotein(a); Mice; Mice, Transgenic; Osteoarthritis; Particle Size; Synovial Fluid; Synovial Membrane

The aim of this study was to investigate the expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with rheumatoid arthritis (RA). Synovial tissues from 9 patients with RA and 5 patients with osteoarthritis (OA) were examined for COX-1 and COX-2 expressions by immunohistochemical staining using 2 polydonal COX-1 and COX-2 antibodies. In RA synovia, synovial lining cells showed intense immunostaining for COX-1, whereas slight to moderate staining was observed in inflammatory cells, stromal fibroblast-like cells and vascular endothelial cells. There was no significant difference in COX-1 expression between RA and OA synovia. The localization of COX-2 expression dearly differed from that of COX-1 expression, being most intense in inflammatory cells. However, there was no difference in COX-1 and COX-2 expressions between RA and OA synovial tissues. Our observations support that inflammatory mechanisms modulated by COX-1 and COX-2 in chronic RA synovium might be similar to those in chronic OA synovium.

Topics: Adult; Aged; Arthritis, Rheumatoid; Cell Division; Cyclooxygenase 1; Cyclooxygenase 2; Female; Fibrin; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Neutrophil Infiltration; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Stromal Cells; Synovial Membrane

Rice bodies are often found in inflammatory joint fluid specimens, especially from rheumatoid arthritis patients, but have rarely been reported in osteoarthritis. We found rice bodies in knee joint fluid specimens from four of 88 patients with osteoarthritis. There were three males and one female. Age ranged from 61 to 86 years. Three patients had slowly progressive knee osteoarthritis and one had rapidly destructive disease. Abundant, recurrent effusions occurred in all four patients despite one to five local corticosteroid injections per patient and radiation synovectomy in two patients. The joint fluid specimens contained 120 to 320 cells/mm3 and large numbers of rice bodies that stained with alizarin red S. Transmission electron microscopy studies showed that the rice bodies were composed of fibrin and contained numerous intra- and extra-cellular calcium crystals composed of apatite alone in two cases and of a combination of apatite and calcium pyrophosphate dihydrate in the two others. Collagen fibers and fragments of bone and cartilage were present in a few rice bodies. Phagocytic cells, type C synoviocytes, chondrocytes and a few inflammatory cells were also seen. These rice bodies composed mainly of fibrin and apatite may have played a role in the pathogenesis of the recurrent joint effusions in our patients.

Topics: Aged; Aged, 80 and over; Apatites; Calcium; Calcium Pyrophosphate; Female; Fibrin; Humans; Knee Joint; Male; Microscopy, Electron; Microscopy, Electron, Scanning Transmission; Middle Aged; Osteoarthritis; Phagocytosis; Synovial Fluid

Fibrin deposition is a prominent finding in the synovium of patients with rheumatoid arthritis (RA). Macrophages are found in increased numbers in RA synovium, and these cells are known to produce a variety of procoagulant and anticoagulant molecules. Using immunohistologic techniques, the content and distribution of several important components of the coagulation system in the synovium of patients with RA, osteoarthritis (OA), or traumatic joint abnormalities requiring surgery were investigated. Samples from 3 patients from each category were examined in detail. RA synovium (compared with that of patients with OA or joint trauma) had increased numbers of macrophages and increased expression/content of fibrinogen, tissue factor, factor XIII, tissue transglutaminase, cross-linked fibrin (fibrin D dimer), urokinase-type plasminogen activator, and alpha 2-plasmin inhibitor. Macrophage content in RA synovium was increased in both the lining cell areas and the interstitial cell areas. Fibrinogen was distributed throughout the tissue in all samples and was greater in RA synovium. In trauma and OA synovia, tissue factor was seen only in association with vessels (endothelial cells), but in RA synovium, it was markedly increased throughout the tissues. While fibrin D dimer was seen in small amounts in synovial lining cell areas of trauma and OA synovia, it was present in increased amounts in the lining cell and interstitial cell areas of RA synovium. Factor XIII and tissue transglutaminase were present in scant amounts in trauma and OA synovia, but there were increased amounts of both (especially tissue transglutaminase) in RA synovium in the vessel, lining cell, and interstitial cell areas. Urokinase and alpha 2-plasmin inhibitor were also markedly increased in RA synovium. These results suggest that in inflamed synovium, there is ongoing extravascular tissue fibrin formation and dissolution that correlates with the degree of inflammation and macrophage content. Extravascular coagulation/fibrinolysis in RA represents a potential target for therapeutic intervention in this disease.

Topics: alpha-2-Antiplasmin; Arthritis, Rheumatoid; Factor XIII; Fibrin; Fibrinogen; Fibrinolytic Agents; Humans; Immunohistochemistry; Macrophages; Osteoarthritis; Plasminogen Activators; Synovial Membrane; Thromboplastin; Transglutaminases; Urokinase-Type Plasminogen Activator

The presence of immunoglobulin and complement deposits in cutaneous blood vessels and at the dermal junction was determined in 34 patients with rheumatoid arthritis (RA). Deposits of IgM and C3 were twice as common in the leg than the arm. The deposits were present in 7/14 patients with extraarticular disease and 1/20 patients with articular disease alone. Deposits of IgM were detected at the dermoepidermal junction in 4 patients with RA. All had circulating antinuclear antibodies.

Topics: Adult; Aged; Antibodies, Antinuclear; Arm; Arthritis, Rheumatoid; Blood Vessels; Complement C3; Female; Fibrin; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoglobulin M; Leg; Lupus Erythematosus, Systemic; Male; Middle Aged; Osteoarthritis; Rheumatoid Factor; Skin

Twenty patients with rheumatoid arthritis (RA) had a biopsy taken from clinically normal skin. These were examined for histological and immunological abnormalities and were compared to those of 8 patients with osteoarthritis (OA). No 'lupus band; linear deposition of immunoglobulin or complement at the dermo-epidermal interface was seen in any patient in either group. Perivascular deposits were seen in 5 out of 20 (25%) patients with RA. These were IgM in all 5 cases with additional C3 in 2 cases (10%) and additional fibrin in one case (5%). No immunoprotein deposits were seen in specimens from any OA patient. 4 of the 5 patients with perivascular immunoprotein deposits had circulating ANAs present and dilutions of 1/256 or higher but normal DNA binding. A sparse perivascular, predominantly lymphocytic infiltrate was seen in 13 out of 20 (65%) patients with RA and 3 of 8 (35%) patients with OA.

Topics: Arthritis, Rheumatoid; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Osteoarthritis; Skin

Topics: Aged; Arthroplasty; Elbow; Elbow Joint; Female; Fibrin; Follow-Up Studies; Hip; Hip Joint; Histocytochemistry; Humans; Joint Prosthesis; Knee; Knee Joint; Male; Microscopy, Electron, Scanning; Middle Aged; Necrosis; Osteoarthritis; Postoperative Complications; Surgical Wound Infection; Synovial Membrane; Time Factors; Wound Healing

Topics: Adult; Aged; Albumins; Arthritis; Arthritis, Rheumatoid; Complement System Proteins; Female; Fibrin; Fibrinogen; Fibrinolysin; Fluorescent Antibody Technique; Humans; Immune Sera; Immunoglobulins; Male; Middle Aged; Osteoarthritis; Synovial Membrane

Topics: Arthritis, Rheumatoid; Blood Sedimentation; Exudates and Transudates; Fibrin; Gangrene; Humans; Osteoarthritis; Polyarteritis Nodosa; Synovial Fluid; Vascular Diseases; Wounds and Injuries