Sclerostin expression in the subchondral bone of patients with knee osteoarthritis.

Abstract

The aim of this study was to assess the expression of β-catenin, transcription factor-4 (TCF-4) and sclerostin in the subchondral bone of patients with primary knee osteoarthritis (OA). Tibial plateau specimens from patients with OA who underwent total knee arthroplasty were classified into the early stage (n=15), intermediate stage (n=13) and late stage (n=17) groups using the Mankin score. Structural parameters, including total articular cartilage (TAC), subchondral bone plate (SCP) thickness and trabecular bone volume (BV/TV), were assessed using Image-Pro Plus 6.0 analysis software. Subsequently, β-catenin and sclerostin expression levels in subchondral bone were determined by immunohistochemistry. In addition, the mRNA and protein levels of β-catenin, TCF-4 and sclerostin were evaluated by RT-qPCR and western blot analysis, respectively. As regards the cartilage and subchondral bone structural parameters, TAC was reduced, while SCP thickness and BV/TV were increased due to OA, with significant differences observed among the different stages (all P<0.05). The results of immunohistochemistry revealed that the β-catenin levels in the intermediate- and late-stage samples were significantly increased, while the levels of sclerostin were markedly decreased compared with the values in the early-stage samples (all P<0.05). Compared with the intermediate-stage samples, the sclerostin levels were decreased, and SCP thickness and the β-catenin levels were increased in the late-stage samples (all P<0.05). The results of RT-qPCR and western blot analysis revealed that the β-catenin and TCF-4 mRNA and protein levels in the intermediate- and late-stage samples were significantly increased, while sclerostin expression was significantly decreased compared with the early-stage samples; a similar trend was observed between the intermediate- and late-stage samples (all P<0.05). Finally, the β-catenin and TCF-4 levels positively correlated with the Mankin scores, while there was a negative correlation with sclerostin expression. Our findings demonstrate that sclerostin expression is closely associated with the degree of joint damage in patients with OA, confirming its involvement in the development of OA.