O-GlcNAc糖基化在肌骨衰减疾病中作用机制研究
Research progress in the mechanism of O-GlcNAc glycosylation in musculoskeletal decay diseases
  
DOI:10.3969/j.issn.1006-7108.2025.11.014
中文关键词:  O-GlcNAc糖基化  骨质疏松症  肌少症  肌骨稳态
英文关键词:O-GlcNAc glycosylation  osteoporosis  sarcopenia  musculoskeletal homeostasis
基金项目:甘肃省中医药管理局科研项目(GZKG-2024-46);甘肃省名中医赵道洲传承工作室建设项目[甘财社(2022)105号];兰州市科技计划项目(2023-2-20,2023-ZD-49)
作者单位
李兴国1 孙兴翔2* 宋承鑫2 刘朝辉1 杨镇源1 彭冉东1 周红1 1.甘肃省中医院甘肃 兰州 730050 2.甘肃中医药大学甘肃 兰州 730000 
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中文摘要:
      O-连接β-N-乙酰葡糖胺(O-GlcNAc)糖基化是一种重要的可逆、动态翻译后修饰。通过O-GlcNAc转移酶(OGT)和O-GlcNAc酶(OGA)动态调节,影响多种细胞过程。近年来随着研究不断深入,发现其在肌、骨代谢疾病中具有重要作用,可参与维持“肌骨稳态”,并调控肌骨衰减疾病的发生发展。因此,本文通过对O-GlcNAc糖基化在肌骨衰减疾病中作用机制研究进行总结,探讨其在骨重塑过程中,通过Wnt/β-catenin途径和Ca2+-PKA-Gfat1轴等途径促进骨形成,调节成骨标志物的表达,维持骨稳态;在早期阶段促进破骨细胞的分化,通过RANKL/TNF-α、NF-κB途径影响氧化磷酸化和细胞-细胞融合等途径,抑制破骨细胞生成,从而减少骨吸收;在肌肉再生方面,通过调控Mef2c和Myogenin表达,促进成肌细胞分化和多核肌纤维形成,维持卫星细胞的健康和功能,促进肌肉修复和再生的作用机制。同时对目前研究中存在的问题进行总结与展望,以期为临床防治肌少-骨质疏松症提供新思路。
英文摘要:
      O-linked beta-n-acetylglucosamine (O-GlcNAc) glycosylation is an important reversible and dynamic post-translational modification. Through the dynamic regulation of O-GlcNAc transferase (OGT) and O-GlcNAc enzyme (OGA), various cellular processes are affected. In recent years, with the deepening of research, it has been found that it plays an important role in muscle and bone metabolic diseases, participates in maintaining musculoskeletal homeostasis, and regulates the occurrence and development of musculoskeletal decay diseases. Therefore, this paper summarizes the mechanism of O-GlcNAc glycosylation in musculoskeletal decay diseases, and explores its role in promoting bone formation, regulating the expression of osteogenic markers, and maintaining bone homeostasis through Wnt/β-catenin pathway and Ca2+-PKA-Gfat1 axis during bone remodeling. O-GlcNAc glycosylation promotes osteoclast differentiation in the early stage, affects oxidative phosphorylation and cell-cell fusion through RANKL/TNF-α,NF-κB pathway, inhibits osteoclast generation, thereby reducing bone resorption. In terms of muscle regeneration, O-GlcNAc glycosylation regulates the expression of Mef2c and Myogenin, promotes the differentiation of myoblasts and the formation of multi-nuclear muscle fibers, maintains the health and function of satellite cells, and promotes the mechanism of muscle repair and regeneration. The problems existing in the current research are summarized and prospected, in order to provide new ideas for clinical prevention and treatment of sarcopenia - osteoporosis.
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