The Role Of Sost Played In Chondrocytes Of Human Osteoarthritis By Wnt/?-catenin Signaling Pathway

Objectives: The purpose of this study is to determine the expression of SOST in cartilage of osteoarthritis(OA) patients and its therapeutic effects on articular cartilage degradation.Methods: All OA human cartilage samples were obtained from OA patients who underwent total knee arthroplasty, and normal cartilage were obtained from patients who underwent amputation. Safranin O staining were used to divide samples in to different groups and SOST were immuno-localized in osteochondral sections of human cartilage samples. Primary human chondrocytes isolated from cartilage were pre-incubated with SOST(250ng/ml) alone or combined with interleukin-1a(IL-1a)(10ng/ml). The activation of Wnt/?-catenin signaling pathway in response to IL-1a, the inhibition in response to SOST,and its effects on the degradation of cartilage were examined by real-time polymerase chain reaction(PCR) and western blotting.Results: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and was detected in the focal area of normal cartilage and mid-stage OA, but there were few SOST staining in the cartilage of end-stage human OA.SOST can inhibit Wnt/?-catenin signaling pathway by binding to LRP5/6 in both normal chondrocytes and OA chondrocytes in vitro but cannot decrease catabolic factors such as RUNX-2, MMP-13, ADAMTS-4,5 in the end-stage human OA chondrocytes as it did in early-stage OA. This suggests that SOST may not have benefit effects on the cartilage in end-stage human OA.Besides,IL-1? can significantly active Wnt/?-catenin signaling pathway and promote the degradation of cartilage, which can be inhibited by SOST in normal cartilage and OA cartilage.Conclusion: SOST was expressed in human cartilage, and was first increased in mid-stage group, but then decreased in end-stage group. Furthermore, increased SOST may play an important role in maintaining cartilage integrity in normal cartilage and early-stage human OA but not in end stage.