It is known that Wnt/β-catenin signaling induces endochondral ossification and plays a significant role in the pathophysiology of osteoarthritis (OA). Sclerostin is a potent inhibitor of the Wnt/β-catenin signaling pathway. This study investigated the role of sclerostin in the endochondral differentiation under an OA-like condition induced by proinflammatory cytokines. ATDC5 cells were used to investigate chondrogenic differentiation and terminal calcification, and 10 ng/ml IL-1β and/or 200 ng/ml sclerostin were added to the culture medium. IL-1β impaired early chondrogenesis from undifferentiated state into proliferative chondrocytes, and it was not altered by sclerostin. IL-1β induced progression of chondrogenic differentiation in the late stage and promoted terminal calcification. These processes were inhibited by sclerostin and chondrogenic phenotype was restored. In addition, sclerostin restored IL-1β-induced upregulation of Wnt/β-catenin signaling in the late stage. This study provides insights into the possible role of sclerostin in the chondrogenic differentiation under the IL-1β-induced OA-like environment. Suppression of Wnt signaling by an antagonist may play a key role in the maintenance of articular homeostasis and has a potential to prevent the progression of OA. Thus, sclerostin is a candidate treatment option for OA.

已知Wnt /β-连环蛋白信号传导诱导软骨内骨化并且在骨关节炎（OA）的病理生理中起重要作用。硬化蛋白是Wnt /β-catenin信号通路的有效抑制剂。这项研究调查了硬化素在促炎性细胞因子诱导的OA样条件下在软骨内分化中的作用。ATDC5细胞用于研究软骨分化和终末钙化，并向培养基中添加10 ng / mlIL-1β和/或200 ng / ml硬化蛋白。IL-1β损害了从未分化状态到增生性软骨细胞的早期软骨形成，并且它没有被硬化素所改变。IL-1β在晚期诱导软骨形成分化，并促进终末钙化。这些过程受到硬化素的抑制，恢复了软骨形成的表型。此外，硬化蛋白在晚期恢复了IL-1β诱导的Wnt /β-catenin信号转导的上调。这项研究提供了关于硬化素在IL-1β诱导的OA样环境下在软骨形成分化中可能发挥作用的见解。拮抗剂抑制Wnt信号可能在维持关节稳态中起关键作用，并有可能预防OA的发展。因此，硬化蛋白是OA的候选治疗选择。拮抗剂抑制Wnt信号可能在维持关节稳态中起关键作用，并有可能预防OA的发展。因此，硬化蛋白是OA的候选治疗选择。拮抗剂抑制Wnt信号可能在维持关节稳态中起关键作用，并有可能预防OA的发展。因此，硬化蛋白是OA的候选治疗选择。