R-spondin2(Rspo2)是蛋白质家族RSPOs成员之一，其可以通过富含亮氨酸重复序列的G蛋白偶联受体4/5(leucine-rich repeat-containing G protein-coupled receptor 4/5，LGR4/5)、细胞表面跨膜 E3 泛素连接酶 ZNRF3/RNF43(zinc and ring finger 3/ring finger protein 43)、硫酸乙酰肝素蛋白聚糖(heparan sulfate proteoglycans，HSPGs)和含 GTP 酶激活蛋白质 1 的 IQ 基序(IQ motif-containing GTPase-activating protein 1，IQGAP1)来调控 Wnt/β 连环蛋白(catenin)信号通路，Wnt/β-catenin信号通路是目前研究最广泛且与基础骨生物学直接相关的信号通路，该通路中任何一环节出现问题都可能对骨的调控产生影响。近年来研究发现，Rspo2可以通过Wnt/β-catenin对成骨细胞(osteoblast，OB)、破骨细胞(osteoclast，OC)和软骨细胞产生作用，并参与一些骨骼疾病如脊柱后纵韧带骨化(ossification of the posterior longitudinal ligament，OPLL)、骨关节炎(osteoarthritis，OA)和类风湿性关节炎(rheumatoid arthritis，RA)的发生发展，因此对Rspo2的研究可能会成为骨相关疾病新的治疗方向。本文结合最新研究进展，就Rspo2的结构和主要功能、Rspo2调控Wnt/β-catenin信号通路的相关机制及其对骨骼系统的影响作一综述，以期为骨相关疾病的防治提供新的思路和途径。
Mechanism of R-spondin2 Regulating Wnt/β-catenin Signaling Pathway and Its Influence on Skeletal System
R-spondin2(Rspo2)is a member of protein family RSPOs,which can be coupled to receptor 4/5(leucine-rich repeat-containing g protein-coupled receptor 4/5,LGR4/5),cell surface transmembrane E3 ubiquitin ligase ZNRF3/RNF43(zinc and ring finger 3/ring finger protein 43),heparan sulfate proteoglycan(heparan sulfate proteoglycans,HSPGs)and the IQ motif(IQ gap 1)containing GTP enzyme activating protein 1,regulating the Wnt/β-catenin signaling pathway,which is the most widely studied signaling pathway and directly related to basic bone biology.Any problem in this pathway may have an impact on bone regulation.In recent years,it has been found that Rspo2 can act on osteoblast,osteoclast and chondrocytes through Wnt/β-catenin,and take part in occureace and development of some bone diseases such as ossification of the posterior longitudinal ligament(OPLL),osteoarthritis(OA)and rheumatoid arthritis(RA),so the study of Rspo2 may become a new therapeutic direction for bone-related diseases.Based on the latest research progress,this paper reviews the structure and main functions of Rspo2,the mechanism of Rspo2 regulating Wnt/β-catenin signaling pathway and its influence on skeletal system,in order to provide new ideas and ways for the prevention and treatment of bone-related diseases.
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维普
