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| R-spondins调控WNT/β-catenin信号通路的机制及其对骨骼系统的影响 |
| The mechanism of R-spondins regulating WNT/β-catenin signaling pathway and and its effect on the skeletal system |
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| DOI：10.3969/j.issn.1006-7108.2021.02.028 |
| 中文关键词: WNT/β-catenin信号通路 R-spondins 骨骼发育 成体骨代谢 |
| 英文关键词:WNT/β-catenin signaling pathway R-spondins skeletal development adult bone metabolism |
| 基金项目:国家自然科学基金（81360400） |
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| 中文摘要: |
| R-spondins是包含凝血酶敏感蛋白1型重复序列[thrombospondin type 1 repeat（TSR-1）-containing proteins]的结构域家族，由四种分泌糖蛋白R-spondin 1-4组成。R-spondins通过富含亮氨酸的G蛋白偶联受体4/ 5/6（leucine-rish repeat-containing G-protein coupled receptor 4/5/6，LGR4/5/6）、细胞表面跨膜E3泛素连接酶ZNRF3[（zinc and ring finger 3）/RNF43 (ring finger protein 43）]、硫酸乙酰肝素蛋白多糖( heparan sulfate proteoglycans，HSPGs）、包含GTPase激活蛋白1（IQ motif containing GTPase-activating protein 1，IQGAP1) 来增强WNT/β-catenin信号通路,进而在人类胚胎发育、组织和器官稳定、干细胞自我更新等方面发挥作用。近年来研究发现R-spondins参与胚胎骨发育、成体骨形成和骨关节疾病的发生发展，对R-spondins的研究可能成为骨代谢疾病新的治疗方向。本文将对R-spondins增强WNT/β-catenin信号通路的相关机制及其对胚胎骨发育、成体骨形成、骨质疏松和骨关节炎相关疾病的影响做一综述。 |
| 英文摘要: |
| R-spondins are a family of domains containing thrombospondin type 1 repeat (TSR-1) -containing proteins, which are composed of four secreted glycoproteins R-spondin 1-4. R-spondins pass through leucine-rish repeat-containing G-protein coupled receptor 4/5/6(LGR4/5/6), cell surface transmembrane E3 ubiquitin ligase Zinc and Ring Finger 3(ZNRF3) /Ring finger protein 43(RNF43), heparan sulfate proteoglycans(HSPGs) , IQ motif containing GTPase-activating protein 1 (IQGAP1) and play a role in human embryo development, tissue and organ stability, and stem cell self-renewal. In recent years, it has been found that R-spondins are involved in embryonic bone development, adult bone formation and the occurrence and development of bone and joint diseases. The research on R-spondins may become a new treatment direction of bone metabolic diseases. In this paper, the mechanism of R-spondins enhancing WNT/β-catenin signaling pathway and its effects on embryonic bone development, adult bone formation, osteoporosis and osteoarthritis related diseases were reviewed. |
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