Abstract
Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of matrix metalloproteinases (MMPs) and enzymes from the a disintegrin and metalloproteinase domain with thrombospondin motifs family in osteoarthritis (OA). Elevated osteopontin (OPN) levels in plasma, synovial fluid and articular cartilage are associated with progressive OA joint damage; however, the role of OPN in the pathological changes of knee OA remains undetermined. The present study was undertaken to examine the effect of OPN on the expression of TIMP-1 and TIMP-2 mRNA in chondrocytes from 16 patients with knee OA. In this study, following the stimulation of human chondrocytes with recombinant human OPN (rhOPN; 100 ng/ml and 1 μg/ml, respectively) for 48 h, MTT assay was used to determine cell viability while the quantitative polymerase chain reaction (PCR) was used to detect the alterations in TIMP-1 and TIMP-2 levels. The results illustrated that neither 100 ng/ml nor 1 μg/ml rhOPN caused cytotoxicity or apoptosis of chondrocytes and that the relative mRNA expression of TIMP-1 and TIMP-2 was significantly increased in the 1 μg/ml rhOPN group compared with that in the control group (P=0.022 and P=0.003, respectively). However, no significant difference in expression was revealed between the 100 ng/ml rhOPN and control groups (P=0.998 and P=0.209, respectively). In conclusion, OPN may have a protective effect against pathological changes in advanced-stage OA.
Highlights
Osteoarthritis (OA), the most prevalent joint disease, is characterised by the progressive breakdown of articular cartilage
Two main enzyme families are believed to be responsible for cartilage destruction in OA: The matrix metalloproteinases (MMPs) mediate cartilage collagen breakdown, whereas enzymes from the a disintegrin and metalloproteinase domain with thrombospondin motifs family mediate loss of cartilage aggrecan
Incubation with human recombinant Tissue inhibitors of metalloproteinases (TIMPs)‐1 or TIMP‐2 inhibited >90% of MMP activity in conditioned media from porcine chondrocytes cultured in the presence of interleukin‐1α [5]
Summary
Osteoarthritis (OA), the most prevalent joint disease, is characterised by the progressive breakdown of articular cartilage. Incubation with human recombinant TIMP‐1 or TIMP‐2 inhibited >90% of MMP activity in conditioned media from porcine chondrocytes cultured in the presence of interleukin‐1α [5]
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