Wnt-β-catenin signaling pathway inhibition by sclerostin may protect against degradation in healthy but not osteoarthritic cartilage

The aim of the present study was to determine the regulation of sclerostin (SOST) in osteoarthritis (OA) and its effect on articular cartilage degradation. Human cartilage samples from healthy and OA subjects were assessed by Safranin O staining and immunohistochemistry. Primary chondrocytes were pre-incubated with 250 ng/ml SOST, 10 ng/ml interleukin-1-alpha (IL-1-alpha) or a combination of the two. The effects of treatment on the Wnt-beta-catenin signaling pathway and cartilage degradation were examined by reverse transcription-quantitative polymerase chain reaction and western blotting. SOST was detected in the cartilage focal area, demonstrating secretion by osteocytes and chondrocytes. SOST has been identified to inhibit the Wnt-beta-catenin signaling pathway by binding to low-density lipoprotein-related receptors 5 and 6, and catabolic factors were decreased in healthy chondrocytes. However, SOST did not influence human OA chondrocytes. IL-1 alpha activated the Wnt-beta-catenin signaling pathway and promoted cartilage degradation, which was inhibited by SOST in healthy and OA cartilage. The results of the present study suggested that SOST is important in maintaining the integrity of healthy, but not end-stage OA, cartilage.