acid-phosphatase and Calcinosis

The review analyses the available evidence on the role of acid and alkaline phosphatases, ATPase as well as non-organic phosphate in the processes of precipitation of insoluble calcium salts in tissues. Participation of phospholipids in this process is noted. The identical role of the ensymatic systems in calcification in the processes of bone formation and in pathological foci including tumours is demonstrated. Exploration of the mechanisms of calcification may be a new step in attempts increasing the effectiveness of human malignant tumours therapy.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adenosine Triphosphate; Alkaline Phosphatase; Animals; Biological Transport, Active; Calcification, Physiologic; Calcinosis; Cartilage; Cell Membrane Permeability; Electric Conductivity; Electron Transport; Energy Metabolism; Humans; Hydroxyapatites; Membrane Lipids; Mitochondria; Neoplasms; Osteogenesis; Oxidative Phosphorylation; Phosphates; Phospholipids; Rats

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 remodeling in calcified aortic valves is thought to originate from microfractures at multiple sites of the valve, at which osteoclasts and osteoblasts are recruited. The aim of the present study was to assess circulating mediators of bone homeostasis, correlate them to the severity of stenosis and explore the spatio-temporal distribution of bone turnover in different parts of calcified aortic valve tissue.. Plasma and explanted aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery. Plasma levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear-κB (RANK) ligand and Runt-related transcription factor 2 (Runx2/Cbfa1) exhibited a significant correlation to the severity of aortic stenosis. mRNA levels in normal, thickened and calcified parts of aortic valves assessed by quantitative real-time PCR were significantly elevated in calcified parts of valves for TRAP (5.08 ± 1.6-fold, P<0.001) RANK ligand (8.6 ± 4.2-fold, P<0.001) and RANK (1.98 ± 0.78-fold, P=0.015). In an age, gender and aortic valve anatomy-adjusted multivariable regression analysis the local transcript levels of TRAP correlated significantly with echocardiographic parameters quantifying stenosis severity in early stages, whereas the expression level of Runx2/Cbfa1 was a predictor of the stenosis severity in advanced stages.. These findings suggest a critical role of bone turnover as a determinant of aortic stenosis severity.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Calcinosis; Core Binding Factor Alpha 1 Subunit; Echocardiography, Doppler; Female; Follow-Up Studies; Gene Expression Regulation; Humans; Isoenzymes; Male; Middle Aged; Osteoclasts; RANK Ligand; Real-Time Polymerase Chain Reaction; RNA; Severity of Illness Index; Tartrate-Resistant Acid Phosphatase

Arterial medial calcification (AMC) is frequent prevalence in patients with end stage renal disease. Evidence about hyperphosphatemia induced anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare. Lanthanum carbonate as an orally administered phosphate-binding agent to reduce phosphate load and ameliorate AMC, but direct evidence is missing.. Detailed time-course studies were conducted of Sprague-Dawley rats fed with adenine and high phosphate diet to imitate the onset and progression of AMC of uremia. Calcification in great arteries was evaluated by VonKossa's and Masson's trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL, Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT-PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit.. Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter group diminished significantly (2.92 ± 0.73 mmol/L vs CRF Group 3.48 ± 0.69, p < 0.01) at week 10. The rats that did not receive 2%La treatment had extensive von kossa staining for medial calcification in CRF group. In contrast, the rats in 2%La group just exhibit mild medial calcification. Inhibitory effect on progression of AMC was reflected by down regulated osteogenic genes and altered osteoclast-like genes. RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF group, p <0.01), whereas marginal difference in serum among the three groups. In contrast to the robust expression of cathepsinK in calcified area, TRAP expression was not found.. Abnormal phosphate homeostasis, induction of osteogenic conversion and osteoclast suppression were contributed to the current mechanisms of uremia associated arterial medial calcification based on our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the decreased phosphate retention and cross-talk between osteoblast and osteoclast-like cell, both of which can be the therapeutic target for uremia associated with AMC.

Topics: Acid Phosphatase; Animals; Calcinosis; Cathepsin K; Core Binding Factor Alpha 1 Subunit; Enzyme-Linked Immunosorbent Assay; Hyperphosphatemia; Isoenzymes; Lanthanum; Osteocalcin; Osteoclasts; RANK Ligand; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Uremia

Vascular calcification is a hallmark of atherosclerosis, a major cause of morbidity and mortality in the United States. We have previously reported that the osteogenic transcription factor Runx2 is an essential and sufficient regulator of calcification of vascular smooth muscle cells (VSMC) in vitro.. To determine the contribution of osteogenic differentiation of VSMC to the pathogenesis of vascular calcification and the function of VSMC-derived Runx2 in regulating calcification in vivo.. SMC-specific Runx2-deficient mice, generated by breeding SM22α-Cre mice with the Runx2 exon 8 floxed mice, exhibited normal aortic gross anatomy and expression levels of SMC-specific marker genes. Runx2 deficiency did not affect basal SMC markers, but inhibited oxidative stress-reduced expression of SMC markers. High-fat-diet-induced vascular calcification in vivo was markedly inhibited in the Runx2-deficient mice in comparison with their control littermates. Runx2 deficiency inhibited the expression of receptor activator of nuclear factor κB ligand, which was accompanied by decreased macrophage infiltration and formation of osteoclast-like cells in the calcified lesions. Coculture of VSMC with bone marrow-derived macrophages demonstrated that the Runx2-deficient VSMC failed to promote differentiation of macrophages into osteoclast-like cells.. These data have determined the importance of osteogenic differentiation of VSMC in the pathogenesis of vascular calcification in mice and defined the functional role of SMC-derived Runx2 in regulating vascular calcification and promoting infiltration of macrophages into the calcified lesion to form osteoclast-like cells. Our studies suggest that the development of vascular calcification is coupled with the formation of osteoclast-like cells, paralleling the bone remodeling process.

Topics: Acid Phosphatase; Animals; Atherosclerosis; Bone Remodeling; Calcinosis; Cell Differentiation; Cells, Cultured; Coculture Techniques; Core Binding Factor Alpha 1 Subunit; Diet, High-Fat; Disease Models, Animal; Exons; Female; Isoenzymes; Macrophages; Male; Mice; Mice, Knockout; Muscle, Smooth, Vascular; Mutagenesis; Osteoclasts; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Clinical and experimental studies demonstrate the important roles of vascular smooth muscle cells (VSMC) in the pathogenesis of atherosclerosis. We have previously determined that the osteogenic transcription factor Runx2 is essential for VSMC calcification. The present study characterized Runx2-regulated signals and their potential roles in vascular calcification.. In vivo studies with atherogenic apolipoprotein E(-/-) mice demonstrated that increased oxidative stress was associated with upregulation of Runx2 and receptor activator of nuclear factor κB ligand (RANKL), which colocalized in the calcified atherosclerotic lesions and were juxtaposed to infiltrated macrophages and osteoclast-like cells that are positively stained for an osteoclast marker, tartrate-resistant acid phosphatase. Mechanistic studies using RNA interference, a luciferase reporter system, chromatin immunoprecipitation, and electrophoretic mobility shift assays indicated that Runx2 regulated the expression of RANKL via a direct binding to the 5'-flanking region of the RANKL. Functional characterization revealed that RANKL did not induce VSMC calcification, nor was RANKL required for oxidative stress-induced VSMC calcification. Using a coculture system, we demonstrated that VSMC-expressed RANKL induced migration as well as differentiation of bone marrow-derived macrophages into multinucleated, tartrate-resistant acid phosphatase-positive osteoclast-like cells. These effects were inhibited by the RANKL antagonist osteoprotegerin and with VSMC deficient in Runx2 or RANKL.. We demonstrate that Runx2 directly binds to the promoter and controls the expression of RANKL, which mediates the crosstalk between calcifying VSMC and migration and differentiation of macrophages into osteoclast-like cells in the atherosclerotic lesions. Our studies provide novel mechanistic insights into the regulation and function of VSMC-derived RANKL in the pathogenesis of atherosclerosis and vascular calcification.

Topics: Acid Phosphatase; Animals; Atherosclerosis; Calcinosis; Cell Differentiation; Cell Movement; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Isoenzymes; Macrophages; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteoclasts; Oxidative Stress; Promoter Regions, Genetic; Protein Binding; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Vascular Diseases

Osteoprotegerin (OPG) inhibits interaction of the receptor-activator of nuclear factor-kappaB (RANK) ligand (RANKL) with its receptor RANK, which is expressed on osteoclasts. OPG appeared to accelerate vascular calcification in vitro by the inhibition of vascular osteoclast-like cells. On the contrary, early-onset arterial calcification was observed in OPG-deficient mice. We measured the coronary artery calcification score (CACS) and abdominal aortic calcification score (AAoCS) by multi-detector computed tomography in 30 pre-dialysis CKD patients (eGFR 20 mL/min on average). Biomarkers were measured, including serum OPG, soluble RANKL (sRANKL) and tartrate-resistant acid phosphatase (TRACP) -5b (the biomarker of osteoclasts independent of renal function). The median values of CACS and AAoCS were 54.4 and 1,088 Agatston units (AU), respectively. Serum OPG was increased and serum sRANKL was decreased. In a multivariate logistic regression analysis using CACS > or = 100 AU as the outcome variable, CACS was found to be positively correlated with serum corrected Ca x iP product and serum OPG, though it was not correlated with serum TRACP-5b. ROC curve analysis showed that the serum OPG cutoff value predicting CACS > or = 100 AU was 5.2 pmol/L (624 pg/mL). In a stepwise regression analysis, log (AAoCS + 1) was positively correlated with serum OPG alone, but it was not correlated with age, eGFR, serum albumin and bone alkaline phosphatase (BAP). No correlation was found between serum OPG and serum TRACP-5b. In conclusion, vascular calcification in pre-dialysis CKD patients was correlated with an increase in OPG, but was independent of serum TRACP-5b. The decrease in serum sRANKL may have been caused by the increase in OPG production.

Topics: Acid Phosphatase; Aorta, Abdominal; Aortic Diseases; Biomarkers; Calcinosis; Coronary Disease; Coronary Vessels; Dialysis; Female; Humans; Isoenzymes; Logistic Models; Male; Osteoclasts; Osteoprotegerin; RANK Ligand; Tartrate-Resistant Acid Phosphatase

To determine the presence of small integrin-binding ligand N-linked glycoprotein (SIBLING) and bone components in juvenile dermatomyositis (DM) pathologic calcifications.. Calcifications were removed from 4 girls with juvenile DM symptoms for mean +/- SD 36.9 +/- 48.3 months and were stained for SIBLING proteins: full-length osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin phosphoprotein (DPP), and matrix extracellular phosphoglycoprotein (MEPE); bone markers: osteocalcin (OC), core-binding factor alpha 1 (CBFalpha1), and alkaline phosphatase (AP) for osteoblasts; tartrate-resistant acid phosphatase (TRAP) for osteoclasts; and the mineral regulators osteonectin (ON) and matrix Gla protein (MGP). The deposit center, periphery, adjacent connective tissue, and vascular endothelial cells were examined.. Alizarin red stained calcified deposits that did not localize with collagen, like bone, under polarized light. Hematoxylin and eosin stain revealed a paucity of connective tissue and absence of bone-like structures. The deposits, connective tissue, and vascular endothelial cells were positive for BSP, DPP, DMP1, and AP; MEPE was not detected. OC, ON, and MGP were present in the deposits and vascular endothelial cells; OPN and CBFalpha1 were present in deposits and connective tissue. TRAP-positive osteoclasts were localized to the calcification periphery.. The disorganized juvenile DM calcifications differ in structure, composition, and protein content from bone, suggesting that they may not form through an osteogenic pathway. Osteoclasts at the deposit surface represent an attempt to initiate its resolution.

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Biomarkers; Calcinosis; Calcium-Binding Proteins; Child; Core Binding Factor Alpha 1 Subunit; Dermatomyositis; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Integrin-Binding Sialoprotein; Isoenzymes; Matrix Gla Protein; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteonectin; Osteopontin; Phosphoproteins; Sialoglycoproteins; Tartrate-Resistant Acid Phosphatase

It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation.. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 microg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor beta (TGF beta), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF beta.. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF beta, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone.. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.

Topics: Acid Phosphatase; Alendronate; Animals; Anterior Cruciate Ligament; Bone Remodeling; Calcinosis; Cartilage, Articular; Collagen; Collagen Type I; Collagen Type II; Disease Models, Animal; Disease Progression; Extracellular Matrix Proteins; Glycoproteins; Isoenzymes; Male; Matrilin Proteins; Osteoarthritis, Knee; Osteoclasts; Peptides; Rats; Sclerosis; Severity of Illness Index; Tartrate-Resistant Acid Phosphatase; Transforming Growth Factor beta

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Calcinosis; Chondrocytes; Femur; Histocytochemistry; Isoenzymes; Mandible; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts; Osteoclasts; Osteogenesis; Parathyroid Hormone-Related Protein; Tartrate-Resistant Acid Phosphatase; Tooth Germ

We examined the effects of long-term bisphosphonate (BP, pamidronate) administration at a therapeutic dose (1.5 mg/kg/day) on the distribution, structure, and vacuolar-type H(+)-ATPase expression of osteoclasts, and the resulting trabecular bone volume and structure in ovariectomized (OVX) mature rats. Six-month-old female rats were allocated to sham-operated control, untreated-OVX, and BP-administered OVX groups. Postoperatively, BP was administered intraperitoneally once a day to OVX rats for up to 30 days. On postoperative days 14, 30, and 60, all of the rats were killed and the distal metaphyseal area of the dissected humeri was examined. Quantitative backscattered-electron image analysis revealed that the trabecular bone volume/unit medullary area in untreated OVX rats was significantly (P < 0.05) lower than that in sham-operated controls at 30 and 60 days postoperation. BP administration significantly (P < 0.05) increased trabecular bone volume at 14, 30, and 60 days postoperation in BP-administered OVX rats compared to both sham-operated and untreated OVX rats. Compared to untreated OVX rats, the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts along the bone trabeculae in BP-administered OVX rats was not significantly decreased on days 14 and 30, but was significantly decreased on day 60. Ultrastructurally, BP administration caused the disappearance of both the ruffled border (RB) and the clear zone (CZ) structures, and decreased the expression of vacuolar-type H(+)-ATPase in most osteoclasts, but did not significantly induce apoptosis of osteoclasts detected by the terminal dUTP nick end-labeling (TUNEL) method. Our results suggest that long-term BP administration significantly reduces bone and calcified cartilage resorption through impairment of the structure and bone-resorbing function of osteoclasts, and thereby effectively maintains trabecular bone volume and structure in ovariectomy-induced acute estrogen deficiency in mature rats.

Topics: Acid Phosphatase; Animals; Apoptosis; Bone Resorption; Calcinosis; Cartilage; Diphosphonates; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humerus; Image Processing, Computer-Assisted; Isoenzymes; Osteoclasts; Ovariectomy; Pamidronate; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; X-Ray Diffraction

Calcifying tendinitis of rotator cuff tendons is a common and painful condition caused by ectopic calcification in humans. To examine the involvement of osteopontin (OPN), a potent regulator of calcium deposition on connective tissues, localization and expression of OPN protein and messenger (m)RNA were investigated in human tissue samples of calcified rotator cuff tendons. Immunohistochemistry demonstrated that OPN was localized in cells surrounding the calcified area. OPN was localized in two distinct cell types, i.e., fibroblast-like cells negative for CD68 and tartrate-resistant acid phosphatase (TRAP) and multinucleated macrophages positive for CD68 and TRAP. In situ hybridization revealed that the mRNA expression of OPN in these cells coincided with the immunohistochemistry results, and these results were supported by reverse transcriptase polymerase chain reaction analysis using human OPN-specific oligonucleotides. Cells located away from the calcified area did not express OPN. The present findings indicate the involvement of OPN in the process of calcification of rotator cuff tendons and suggest that OPN plays a role in such painful disorders through the actions of at least two cell types.

Topics: Acid Phosphatase; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Arthrography; Calcinosis; Female; Fibroblasts; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes; Macrophages; Middle Aged; Osteopontin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rotator Cuff; Sialoglycoproteins; Tartrate-Resistant Acid Phosphatase; Tendinopathy; Tendons

High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG(-/-) mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG(-/-) mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG(-/-) mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-kappaB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG(-/-) mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.

Topics: Acid Phosphatase; Animals; Aorta; Blotting, Western; Bone Density; Calcinosis; Cathepsin K; Cathepsins; CHO Cells; Cricetinae; Femur; Glycoproteins; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes; Mice; Mice, Knockout; Mice, Transgenic; NF-kappa B; Osteoclasts; Osteopetrosis; Osteoporosis; Osteoprotegerin; Radiography; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Tartrate-Resistant Acid Phosphatase

To elucidate the process of ossification in spinal ligaments, an aqueous solution containing recombinant human bone morphogenetic protein (BMP)-2 (40 micrograms/100 microL) was injected into murine ligamenta flava, and the ossification process was analyzed morphologically. In the control group, the solution administered lacked the protein; these flattened ligamentous fibroblasts possessing BMP receptors type IA and type II existed among type I collagen bundles. In the week immediately following the injection of BMP-2, ligamentous fibroblasts began to proliferate, differentiating into alkaline phosphatase-positive chondrocytes surrounded by an extracellular matrix composed of type I and II collagen. By the second week, differentiated chondrocytes of various stages were observed in type II collagen-rich matrix. These chondrocytes showed an abundance of BMP receptors type IA and II. The pathologically induced cartilage was resorbed by chondroclasts, permitting migration of blood vessels and osteogenic cells, as well as providing a site for endochondral ossification. By the third week, BMP-induced ossification had compressed the spinal cord, and by the sixth week, the ligamentous tissue had been almost completely replaced by bone. Ligamentous fibroblasts appeared to possess BMP receptors, as well as the potentiality to differentiate into chondrocytes. BMP receptors were upregulated during chondrification of ligamentous fibroblasts induced by exogenous BMP-2, suggesting that BMPs may play an important role in ossification of spinal ligaments.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins; Calcinosis; Cartilage; Cell Differentiation; Collagen; Extracellular Matrix; Fibroblasts; Humans; Immunohistochemistry; Isoenzymes; Ligamentum Flavum; Lumbar Vertebrae; Male; Mice; Protein Serine-Threonine Kinases; Receptors, Growth Factor; Recombinant Proteins; Ribonucleases; Tartrate-Resistant Acid Phosphatase; Transforming Growth Factor beta

The expression of some candidate osteoclast markers, tartrate-resistant acid phosphatase (TRAP), macrophage associated antigens (M phi Ag), and vitronectin receptor (VNR) on foreign body giant cells (FBGCs) was investigated in peri-implant tissues of loosened total joint arthroplasties. Osteoclasts showed distinct staining characteristics. They were strongly TRAP-positive at tartrate concentrations of 50-200 mM and expressed VNR and a restricted range of M phi Ag. In contrast, FBGCs were shown to be significantly heterogeneous. Significant numbers of FBGCs were TRAP-positive at a 100 mM tartrate concentration and some were more intense than osteoclasts. A population of FBGCs did not express M phi Ag such as CD11b, but expressed VNR. It was demonstrated that these candidate osteoclast markers were also positive on FBGCs. These results have highlighted the difficulty in distinguishing these two cell lineages and suggested that there might be some uncertainty in defining osteoclast-like cells in culture studies.

Topics: Acid Phosphatase; Antigen-Antibody Reactions; Antigens, Differentiation; Arthroplasty; Biomarkers; Bone Resorption; Calcinosis; Cells, Cultured; Femur; Foreign Bodies; Galectin 3; Giant Cells; Granuloma, Foreign-Body; Histocytochemistry; Humans; Immunohistochemistry; Integrins; Macrophages; Membrane Glycoproteins; Osteoclasts; Prostheses and Implants; Receptors, Cytoadhesin; Receptors, Vitronectin; Tibia

The propensity of crosslinked collagen matrices to calcify when implanted in animals and human beings is well documented. This article demonstrates that the covalent binding of the biphosphonate, 3-amino-1-hydroxy-propane-1-1-diphosphonic acid, to active bone matrix inhibits bone formation as well as dystrophic calcification. The inhibitory effects on calcium accumulation and alkaline phosphatase activity are greater than those achieved by inactivation of the matrix by protease digestion of the bone morphogenetic factors present in demineralized bone. Whereas bone formation is a cell-mediated effect, artificially crosslinked collagen matrices calcify extensively inside diffusion chambers, reflecting a non-cell-mediated nucleation process. The fundamental differences described should shed light on new modalities to modulate these processes in living systems.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Demineralization Technique; Bone Diseases, Metabolic; Bone Transplantation; Calcinosis; Collagen; Diphosphonates; Femur; Humans; Male; Models, Biological; Osteocalcin; Pamidronate; Protein Binding; Rats; Tibia

This study evaluates the progression of osteoarthritis (OA) in the adult New Zealand white rabbit temporomandibular joint following unilateral disc perforation. Thirty-seven animals were divided into five groups: control (n = 8), 6-week sham (n = 5), and experimental 6-, 12-, and 24-weeks (n = 8 each). Quantitative data was examined with two-way analysis of variance, and followed by Scheffe pair-wise comparisons. Transmission electron microscopy, acid phosphatase [AcP] activity, uronic acid content, and gross morphologic analysis indicated that disc perforation induced remodeling activity and degenerative changes in the condylar cartilage and bone as early as 6 weeks postoperatively. AcP activity of homogenized cartilage samples was significantly increased in experimental joints versus the side that did not undergo surgery at 6 and 12 weeks (P < .05). Uronic acid content was significantly greater in experimental joints versus the side that did not undergo surgery at 6 weeks (P < .05). Heightened cellular activity was present in the deep zone of osteoarthritic fibrocartilage of the 6- and 12-week experimental groups. Degenerating chondrocytes appeared to contain greater proportions of intracytoplasmic filaments and lysosome-like bodies. Disc perforation provided the impetus for degenerative or remodeling changes in the condylar cartilage of experimental joints, and is consistent with secondary OA. These dynamic events were most significant in the deep zone of articular fibrocartilage.

Topics: Acid Phosphatase; Animals; Body Water; Bone Remodeling; Calcinosis; Cartilage, Articular; Collagen; Cytoplasm; Elastic Tissue; Endoplasmic Reticulum; Glycosaminoglycans; Golgi Apparatus; Mandibular Condyle; Microscopy, Electron; Osteoarthritis; Rabbits; Temporomandibular Joint; Time Factors; Tissue Adhesions; Uronic Acids

Samples of deposits taken from sites close to articulations in a young black African suffering from tumoral calcinosis with hyperphosphoraemia were studied by light and electron microscopy techniques. Light microscopy demonstrated lesions of a foreign body granuloma type in contact with calcium salt deposits suggesting that the process was of an active nature. Electron microscopy, and the demonstration of acid phosphatase activity, led to the identification of two cell types: mono or multinuclear macrophage type cells which phagocytose the deposit, and fibroblastic type cells. No signs of damage to the microvessels or the interstitial collagen were noted which could serve as a basis or a physiopathological explanation of the deposition. The deposits were analysed by energy dispersive X-ray microanalysis and by electron diffraction and were considered to be hydroxyapatite.

Topics: Acid Phosphatase; Adult; Calcinosis; Electron Probe Microanalysis; Histocytochemistry; Humans; Lysosomes; Macrophages; Male; Microscopy, Electron; Muscles

An investigation was undertaken to study the distribution of enzymes associated with submandibular gland salivary calculi. Ten calculi were freeze-sectioned and incubated for acid and alkaline phosphatases and for lactate, succinate and maleate dehydrogenases. All calculi were partly covered by a 50-210 micrometers wide zone of organic material consisting of connective tissue and metaplastic squamous epithelium facing the mineralized calculus, or of a structureless substance attached to the mineralized calculus. The epithelium showed an intense staining reaction for acid phosphatase and lactate dehydrogenase and a moderate reaction for succinate dehydrogenase throughout all levels of the epithelium. The structureless peripheral zone exhibited a moderate activity of acid phosphatase and succinate dehydrogenase located to an area close to the mineralized matrix. Also alkaline phosphatase and lactate dehydrogenase were found in a special pattern in the structureless zone. Sodium fluoride and sodium vanadate added to the incubation medium inhibited acid phosphatase activity whereas cupric chloride only lowered the staining reaction. Enzyme activity was found only within the peripheral zone of organic material with one exception. The results suggest that the calcification process of salivary calculi is not a passive calcification of necrotic material or mucin but rather an active process promoted by enzymes in the surrounding organic substances.

Topics: Acid Phosphatase; Alkaline Phosphatase; Calcinosis; Humans; L-Lactate Dehydrogenase; Malate Dehydrogenase; Salivary Duct Calculi; Succinate Dehydrogenase

In this paper, studies by a large series of independent investigators are reviewed with regard to the basic structure and function of the prostate in an attempt to examine their relationship to prostatic cancer etiology. These studies demonstrate that the functional activities of the prostate involve secretion, transport, and reabsorption of a variety of materials into and out of the glandular lumen and that these activities are directly related to the basic structural organization of the gland. These functional activities are constantly occurring in the prostate even under basal (ie, nonejaculating) conditions. Due to these functional activities, the prostatic fluid in the glandular lumen is a complex mixture of a variety of components derived, not only from the synthetic activity of the glandular epithelial cells of the gland itself, but also from the blood serum. The levels of these components are continuously modulated, not only by the frequency of active ejaculation, but also, under basal conditions by the continuous interaction with the glandular prostatic cells lining the acinar lumen and ducts. A concept is presented that the initiation and/or promotion of prostatic carcinogenesis may well involve the chronic modulation/interaction of the prostatic glandular cells with their lumenal fluid.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aging; Animals; Body Fluids; Calcinosis; Dogs; Ejaculation; Electric Stimulation; Electrolytes; Humans; Male; Middle Aged; Mucous Membrane; Organ Size; Prostate; Prostatic Neoplasms; Proteins; Rats; Seminal Vesicles

Nine lysosomal enzymes and alkaline phosphatase have been assayed in human pancreatic juice from controls and patients with chronic calcifying pancreatitis. Specific activities were evaluated by a nonparametric test (Wilcoxon) with a probability of 2 P less than or equal to 0.5. The values of acid phosphatase, alpha-glucosidase, beta-glucosidase and alpha-galactosidase are significantly higher in pathological juices; the values of alpha-mannosidase and beta-glucuronidase are also increased in the same patients but at the limit of significance. Alkaline phosphatase, beta-hexosaminidase and alpha-fucosidase follows the same trend but the values are not statistically significant between the two groups of patients. Studies on skin cultures of four patients with chronic calcifying pancreatitis demonstrate that the increased specific activities of lysosomal enzymes in the pathological juices do not correspond to a leakage of these enzymes into the extracellular space as described for cystic fibrosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; alpha-Glucosidases; Calcinosis; Cells, Cultured; Chronic Disease; Cystic Fibrosis; Fibroblasts; Humans; Hydrolases; Lysosomes; Pancreatic Juice; Pancreatitis

Aortic medial calcification was investigated in rats in which the progeria-like syndrome (PLS) was evoked by administering dihydrotachysterol. In 35 experimental rats and 15 controls, calcification was studied morphologically by light and electron microscopy, and by enzyme histochemistry. Body weight, food intake and serum calcium levels were also determined. Calcification occurred along and on the elastic lamellae in association with the accumulation of ground substance. In the smooth-muscle cells surrounding the calcified foci, the activities of various lysosomal enzymes increased concomitantly with a tendency toward transformation of smooth-muscle cells to a modified form. From these observations, the role of ground-substance formation by smooth-muscle cells is postulated, and participation in the catabolism of ground substance by the lysosomal enzymes of these cells is suggested. It appears the increased activity of adenosine monophosphatase should be linked to the calcification. The etiology of weight loss, skin manifestations and aortic calcification in PLS rats seems to be different from that in human progeric diseases. Therefore, the PLS rat should not be readily accepted as an animal model for the study of progeric diseases.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Aorta; Aortic Diseases; Apyrase; Body Weight; Calcinosis; Calcium; Dihydrotachysterol; Female; Glucuronidase; Hexosaminidases; Histocytochemistry; Phosphoric Monoester Hydrolases; Rats; Werner Syndrome

Topics: Acid Phosphatase; Acute Kidney Injury; Alkaline Phosphatase; Animals; beta-Aminoethyl Isothiourea; Calcinosis; Depression, Chemical; Electron Transport Complex IV; Histocytochemistry; Injections, Intraperitoneal; Kidney; Kidney Tubular Necrosis, Acute; Kidney Tubules, Proximal; Loop of Henle; Male; Nephrosclerosis; Nephrosis; Rats; Rats, Inbred Strains; Succinate Dehydrogenase; Time Factors

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Calcinosis; Infertility, Male; Male; Manganese Poisoning; Rabbits; Succinate Dehydrogenase; Testis

Topics: Acid Phosphatase; Alveolar Process; Ameloblasts; Animals; Bone and Bones; Bone Resorption; Calcinosis; Calcium; Copper; Female; Fluorides; Histocytochemistry; Molybdenum; Odontoblasts; Osteoclasts; Rats; Tartrates; Tooth; Tooth Eruption; Vanadium; Vitamin D

Topics: Acid Phosphatase; Alkaline Phosphatase; Calcinosis; Calcium; Female; Humans; Male; Phosphates; Skin Diseases; Urea

Topics: Acid Phosphatase; Aged; Albumins; Alkaline Phosphatase; Asbestos; Asbestosis; Blood Protein Electrophoresis; Calcinosis; Calcium; Globulins; Humans; Magnesium; Middle Aged; Occupational Diseases; Phosphorus; Pleural Diseases; Radiography

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Calcinosis; Citrates; Ergocalciferols; Esterases; Histocytochemistry; Male; Microscopy, Electron; Periodontium; Rats; Sodium; Succinate Dehydrogenase; Time Factors

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Blood; Calcification, Physiologic; Calcinosis; Eggs; Osteoblasts; Osteoclasts; Periodicity; Poultry; Research

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone and Bones; Bone Marrow; Breast Neoplasms; Calcinosis; Calcium; Cortisone; Dihydrotachysterol; Estrone; Femur; Humans; Hydrocortisone; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Neoplasm Transplantation; Pharmacology; Rats; Research