镁通过调控Wnt/β-catenin通路抑制软骨基质降解防治骨关节炎的机制研究

Osteoarthritis (OA) is a common chronic joint disease characterized by cartilage degeneration. The degradation of cartilage extracellular matrix is one of its major pathological changes. Our previous research indicated that serum magnesium (Mg) concentration was inversely associated with the prevalence of OA. Mg increased the expression of type Ⅱ collagen, inhibited the degradation of human cartilage extracellular matrix and delayed the progression of OA in a rat model. However the mechanism remains unclear. Over-expression of Wnt/β-catenin signaling pathway played an important role in cartilage extracellular matrix degradation and OA development. Meanwhile, it was found in our pilot experiment that Mg down-regulated the expression of β-catenin protein. Therefore, we speculated that Mg could inhibit the degradation of cartilage extracellular matrix and prevent OA by regulating Wnt/β-catenin pathway. In this project, we intend to verify this hypothesis and to research related molecular mechanisms in vitro and in vivo by using over-expression transfection, siRNA interference, qRT-PCR, Western Blot, immunohistochemistry and other techniques. Our study will provide new insights into OA prevention and treatment.

骨关节炎（osteoarthritis，OA）是一种常见的以软骨退行性病变为主要表现的慢性关节疾病，软骨细胞外基质降解是其重要的病理变化。申请人团队前期研究发现血镁浓度较高的人群OA患病率较低，补充镁可促进Ⅱ型胶原表达、抑制软骨细胞外基质降解，并可延缓OA大鼠关节软骨退变，但机制尚不明确。Wnt/β-catenin信号通路过表达可诱导软骨细胞外基质降解，在OA发生发展过程中起重要作用。同时，申请人团队通过预实验发现镁可降低β-catenin蛋白表达。因此申请人推测抑制Wnt/β-catenin通路在补镁防治OA的机制中发挥重要作用。本项目拟采用过表达转染、siRNA干扰、qRT-PCR、Western Blot、免疫组化等技术，在体外细胞和模式动物层面明确镁通过调控Wnt/β-catenin通路抑制软骨细胞外基质降解，从而延缓OA发生发展，并探讨相关分子机制，为临床防治OA提供新思路。

骨关节炎（osteoarthritis，OA）是一种常见的以软骨退行性病变为主要表现的慢性关节疾病，软骨细胞外基质降解是其重要的病理变化。申请人推测抑制Wnt/β-catenin通路在补镁防治OA的机制中发挥重要作用。为证实这一个推测，本项目开展动物实验，采用半月板失稳术(destabilization of the medial meniscus, DMM)构建小鼠膝骨关节炎（osteoarthritis, OA）模型，通过改变饲料中的镁的含量进行低镁干预，之后通过病理切片、翻红固绿染色检测软骨退变程度，从而研究了低镁对OA软骨的影响。在此基础上开展细胞实验，通过更改培养基中镁的含量干预体外培养的软骨细胞，探究了低镁影响OA的分子机制，明确了低镁对软骨细胞Wnt/β-catenin信号通路的影响。本项目明确镁对OA的预防和治疗作用，为OA临床防治提供新思路。