成骨细胞旁分泌Rspo2调控软骨下骨重塑在骨关节炎发病机制中的作用

骨关节炎（OA）发病机制复杂，病理改变涉及整个关节，其中，软骨下骨重塑在OA发病中的作用日益受到重视，但作用机制尚未阐明。研究表明Wnt/β-catenin介导的成骨细胞功能改变可能是OA软骨下骨重塑的重要因素。我们前期通过基因芯片筛选和预实验证实近年来新发现的调控Wnt/β-catenin的信号分子R-spondin2(Rspo2)在OA软骨下骨存在表达差异，提示Rspo2可能通过Wnt/β-catenin介导参与OA软骨下骨重塑。本课题拟利用分子生物学、组织学检测等方法明确Rspo2在OA软骨下骨的表达情况，通过敲低和过表达成骨细胞Rspo2和体外细胞共培养模型探讨Rspo2对软骨下骨重塑的影响及作用机制。最后，应用小鼠OA模型、基因敲除小鼠验证Rspo2-LGR-Wnt/β-catenin轴在OA发病中的作用，为软骨下骨重塑在OA发病中的作用机制提供新的认识，为防治OA提供新的靶点。

The pathogenesis of osteoarthritis (OA) is complex. Pathological changes involve the whole joint. Among them, the role of subchondral bone remodeling in the pathogenesis of OA has attracted more and more attention, but the specific mechanism has not yet been elucidated. Studies have shown that changes in osteoblast function mediated by Wnt/β-catenin may be involved in subchondral bone remodeling of OA. In our preliminary study, gene chip screening and preliminary experiments confirmed that R-spondin2 (Rspo2), a newly discovered signalling molecule regulating Wnt/β-catenin, was differently expressed in subchondral bone in OA, indicating that Rspo2 may be involved in subchondral bone remodeling of OA via Wnt/β-catenin. In this project, the expression and localization of Rspo2 in subchondral bone of OA will be determined by molecular biology, histological detection and other methods. The effect and mechanism of Rspo2 on subchondral bone remodeling will be investigated by knockdown and overexpression of osteoblast Rspo2 and in vitro co-culture model. Finally, the role of Rspo2-LGR-Wnt /β-catenin axis in regulating the pathogenesis of OA will be verified by the mouse OA models and gene knockout mice. These studies will provide a new understanding of the mechanism of subchondral bone remodeling in the pathogenesis of OA, and provide a new target for the prevention and treatment of OA.