《生命科学》 2022, 34(12): 1519-1529

Wnt/β-catenin信号通路在运动调控骨形成中的机制

郭一览^1,2 , 孙　朋^1,2,*

¹华东师范大学体育与健康学院，上海 200241 ²华东师范大学青少年 健康评价与运动干预教育部重点实验室，上海 200241

摘　要：

骨形成是成骨细胞(osteoblast, OB) 合成和分泌骨基质，进而矿化形成新骨的过程。研究表明，运动能够通过外部机械应力、机体内分泌激素水平调节、表观遗传等方式调控骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMSCs) 分化命运，促进骨形成，在不同生理、病理条件下改善骨量。Wnt/β-catenin 信号通路与“运动因子”交互作用，既能通过抑制骨硬化蛋白(osteosclerosis, SOST) 和Dickkopf相关蛋白1 (Dickkopf-related protein 1, DKK1)，促进Wnt 配体及其受体(LRP5/6) 基因的表达，激活β-catenin下游信号转导；也能通过促进和( 或) 抑制相关细胞因子和激素的分泌及调控非编码RNA (non-coding RNA, ncRNA) 等方式，间接激活Wnt/β-catenin 信号通路。该文系统梳理了不同形式的运动对Wnt/β-catenin通路的调控作用，探讨了该通路在运动调控骨形成过程中的具体作用机制，以期为运动防治骨代谢相关疾病及药物靶点的研发提供理论参考。

通讯作者：孙　朋 , Email:psun@tyxx.ecnu.edu.cn

Mechanism of Wnt/β-catenin signaling pathway in motion regulation of bone formation

GUO Yi-Lan^1,2 , SUN Peng^1,2,*

¹College of Physical Education and Health, East China Normal University, Shanghai 200241, China ²Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, China

Abstract:

Bone formation is a process in which osteoblasts (OB) synthesize and secrete bone matrix, and then mineralize to form new bone. Studies have shown that exercise can regulate the differentiation fate of bone marrow mesenchymal stem cells (BMSCs) through external mechanical stress, regulation of endocrine hormone levels and epigenetic modifications, promote bone formation, and improve bone mass under different physiological and pathological conditions. Wnt/β-catenin signaling pathway interacts with exerkines, which can promote the expression of Wnt ligand and its receptor (LRP5/6) gene and activate the downstream signal transduction of β-catenin by inhibiting osteosclerosis sclellosin (SOST) and Dickkopf-related protein 1 (DKK1). It can also indirectly activate Wnt/β-catenin signaling pathway by promoting and/or inhibiting the secretion of related cytokines and hormones and regulating non-coding RNAs (ncRNAs). Here we systematically sorting out the regulatory effects of different forms of exercise on Wnt/β-catenin pathway and exploring its specific roles in exercise-regulated bone formation, aiming to provide theoretical references for treatment of bone metabolismrelated diseases by exercise and development of potential drug targets.

Communication Author：SUN Peng , Email:psun@tyxx.ecnu.edu.cn