acid-phosphatase and Osteoarthritis--Knee

To assess the activity of arylsulfatase (AS), acid phosphatase (ACP), cathepsin D (CAT-D) and alpha-1 antitrypsin (AAT) in blood serum and synovial fluid (SF) of patients with hip or knee osteoarthritis (OA).. The study included 43 subjects with OA (35 hip OA, 8 knee OA), submitted total joint replacement. The control group consisted of 58 subjects with no past history of musculoskeletal disorders.. The OA blood serum samples showed a significantly higher level of lysosomal enzymes activity than in the control group (AS by 17.8%, AAT by 42.4%); only the CAT-D activity decreased by 50%). AS, ACP and CAT-D activities were about two-fold higher in SF when compared with blood of OA patients. The differences between the genders were visible in the SF: Total protein concentration, activity of ACP (both higher in OA men) and activity of CAT-D (higher in OA women). Between the involved hip and knee, there were no significant differences in all estimated parameters in the blood serum of the OA group. In regard to the SF, only ACP activity was significantly higher in patients with a hip involved.. The osteoarthritic SF enzymatic profile differs from that in normal joints. The OA in joints is not reflected in the systemic response. Our preliminary results suggest further studies on role of lysosomal enzymes (ACP and AS) as biomarkers for the detection of osteoarthritis.

Topics: Acid Phosphatase; Adult; Aged; alpha 1-Antitrypsin; Arylsulfatases; Case-Control Studies; Cathepsin D; Female; Humans; Lysosomes; Male; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Reference Values; Synovial Fluid

Subchondral bone cyst (SBC) growth, caused by osteoclast activity during early knee osteoarthritis (OA) pathogenesis, should be treated to prevent further progressions of OA. In the present study, we evaluated the effects of gentle treadmill walking on subchondral bone and cartilage changes in an experimental rat model of destabilized medial meniscus (DMM).. Twelve-week-old Wistar rats underwent DMM surgery in their right knee and sham surgery in their left knee and were assigned to either the sedentary group or walking group (n = 42/group). Animals in the walking group were subjected to treadmill exercise 2 days after surgery, which included walking for 12 m/min, 30 min/day, 5 days/week for 1, 2, and 4 week(s). Subchondral bone and cartilage changes were evaluated by micro-CT analysis, histological analysis, and biomechanical analysis.. Treadmill walking had a tendency to suppress SBC growth, which was confirmed by micro-CT (P = 0.06) and positive staining for tartrate-resistant acid phosphatase (TRAP) activity for the osteoclast number per bone surface (P = 0.09) 4 weeks after surgery. These changes coincide with the prevention of cartilage degeneration as evaluated by the Osteoarthritis Research Society International (OARSI) score (P < 0.05) and biomechanically softening (P < 0.05). Furthermore, treadmill walking could suppressed increasing osteocyte deaths (P < 0.01), which was positively correlated with the OARSI score (r = 0.77; P < 0.01).. These results indicate biomechanical and biological links exist between cartilage and subchondral bone; preventive effects of treadmill walking on subchondral bone deterioration might be partly explained by the chondroprotective effects.

Topics: Acid Phosphatase; Animals; Apoptosis; Cartilage, Articular; Cell Death; Disease Models, Animal; Exercise Test; Immunohistochemistry; In Situ Nick-End Labeling; Male; Menisci, Tibial; Osteoarthritis; Osteoarthritis, Knee; Osteocytes; Osteophyte; Rats; Rats, Wistar; Tibia; Walking; X-Ray Microtomography

Several studies have shown that cathepsin K (CTK) is overexpressed in osteoarthritic (OA) cartilage and subchondral bone. However, it has not been well established whether CTK expression is harmful or beneficial. We undertook this study to investigate the direct involvement of CTK in OA development using Ctsk-knockout (Ctsk(-/-)) mice in a joint instability-induced model of OA.. We analyzed the natural course of the phenotype of 25-week-old Ctsk(-/-) mice. OA development was evaluated with a modified Mankin histologic score up to 8 weeks after surgery was performed to destabilize the knee in Ctsk(-/-) and Ctsk(+/+) mice. Histologic analysis was used to evaluate expression of CTK, matrix metalloproteinase 13 (MMP-13), ADAMTS-5, and tartrate-resistant acid phosphatase (TRAP) proteins in chondrocytes, synovial cells, and osteoclasts. Bone architecture was analyzed by histomorphometry.. Bone mineral content and bone volume were higher in Ctsk(-/-) mice at 25 weeks, whereas OA did not develop spontaneously in either Ctsk(-/-) or Ctsk(+/+) mice. In a model of destabilization-induced OA, OA progression was significantly delayed in Ctsk(-/-) mice. CTK was overexpressed in chondrocytes and synovial cells of knee joints developing OA in Ctsk(+/+) mice. MMP-13 and ADAMTS-5 were less strongly expressed in chondrocytes of Ctsk(-/-) mice, and MMP-13 was less strongly expressed in synovial cells. TRAP-positive osteoclasts were overexpressed in Ctsk(-/-) mice.. These results indicate that CTK plays crucial direct roles in the early to intermediate stage of OA development. CTK-positive chondrocytes and synovial cells may be a possible target to prevent disease progression in OA.

Topics: Acid Phosphatase; ADAM Proteins; Animals; Bone and Bones; Bone Density; Cartilage, Articular; Cathepsin K; Chondrocytes; Disease Models, Animal; Disease Progression; Isoenzymes; Knee Joint; Matrix Metalloproteinase 13; Mice; Mice, Knockout; Osteoarthritis, Knee; Osteoclasts; Phenotype; Synovial Membrane; Tartrate-Resistant Acid Phosphatase

Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeostasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, immunohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the osteocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogenesis.

Topics: Acid Phosphatase; Aged; Apoptosis; Bone Remodeling; Cell Count; Cell Shape; Female; Gene Expression Profiling; Humans; Isoenzymes; Male; Matrix Metalloproteinases; Microscopy, Electron, Scanning; Middle Aged; Osteoarthritis, Knee; Osteocytes; Osteosclerosis; Phenotype; Real-Time Polymerase Chain Reaction; Staining and Labeling; 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

Interleukin-1beta and tartrate resistant acid phosphatase concentrations in synovial fluid aspirates were examined to determine if they could be used as indicators of increased synovial inflammation and an osteolytic reaction in patients having total knee arthroplasty. Synovial aspirates were obtained from seven patients with severely osteoarthritic knees that were scheduled for primary total knee arthroplasty and from 20 patients with knees scheduled for total knee arthroplasty revision. Eleven of the revision cases involved titanium alloy prostheses and nine involved cobalt chrome alloy prostheses. The interleukin-1beta and tartrate resistant acid phosphatase concentrations were obtained and compared between the group having primary total knee arthroplasty and the group having revision total knee arthroplasty. The knees having revision surgery had higher concentrations of interleukin-1beta and tartrate resistant acid phosphatase than did the knees having primary total knee arthroplasty. These results indicate a greater inflammatory and osteolytic response in knees having revision surgery. Although the osteoarthritic knees and the knees needing revision surgery in this study are considered to have an inflammatory state, it was only after total knee arthroplasty when particulate wear debris would be present that appreciable concentrations of interleukin-1beta and tartrate resistant acid phosphatase were produced.

Topics: Acid Phosphatase; Arthroplasty, Replacement, Knee; Biomarkers; Humans; Interleukin-1; Isoenzymes; Knee Prosthesis; Osteoarthritis, Knee; Osteolysis; Reoperation; Synovial Fluid; Tartrate-Resistant Acid Phosphatase