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骨稳态与骨质疏松中的翻译后修饰

Posttranslational Modification in Bone Homeostasis and Osteoporosis.

作者信息

Lin Yuzhe, Jiang Shide, Yao Yuming, Li Hengzhen, Jin Hongfu, Yang Guang, Ji Bingzhou, Li Yusheng

机构信息

Department of Orthopedics Xiangya Hospital Central South University Changsha China.

Xiangya School of Medicine Central South University Changsha China.

出版信息

MedComm (2020). 2025 Apr 1;6(4):e70159. doi: 10.1002/mco2.70159. eCollection 2025 Apr.

Abstract

Bone is responsible for providing mechanical protection, attachment sites for muscles, hematopoiesis micssroenvironment, and maintaining balance between calcium and phosphorate. As a highly active and dynamically regulated organ, the balance between formation and resorption of bone is crucial in bone development, damaged bone repair, and mineral homeostasis, while dysregulation in bone remodeling impairs bone structure and strength, leading to deficiency in bone function and skeletal disorder, such as osteoporosis. Osteoporosis refers to compromised bone mass and higher susceptibility of fracture, resulting from several risk factors deteriorating the balanced system between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. This balanced system is strictly regulated by translational modification, such as phosphorylation, methylation, acetylation, ubiquitination, sumoylation, glycosylation, ADP-ribosylation, S-palmitoylation, citrullination, and so on. This review specifically describes the updating researches concerning bone formation and bone resorption mediated by posttranslational modification. We highlight dysregulated posttranslational modification in osteoblast and osteoclast differentiation. We also emphasize involvement of posttranslational modification in osteoporosis development, so as to elucidate the underlying molecular basis of osteoporosis. Then, we point out translational potential of PTMs as therapeutic targets. This review will deepen our understanding between posttranslational modification and osteoporosis, and identify novel targets for clinical treatment and identify future directions.

摘要

骨骼负责提供机械保护、肌肉附着位点、造血微环境,并维持钙和磷之间的平衡。作为一个高度活跃且动态调节的器官,骨形成与骨吸收之间的平衡在骨骼发育、受损骨修复和矿物质稳态中至关重要,而骨重塑失调会损害骨骼结构和强度,导致骨功能缺陷和骨骼疾病,如骨质疏松症。骨质疏松症是指骨量受损和骨折易感性增加,这是由多种风险因素破坏了成骨细胞介导的骨形成和破骨细胞介导的骨吸收之间的平衡系统所致。这个平衡系统受到翻译后修饰的严格调控,如磷酸化、甲基化、乙酰化、泛素化、SUMO化、糖基化、ADP-核糖基化、S-棕榈酰化、瓜氨酸化等。本综述特别描述了有关翻译后修饰介导的骨形成和骨吸收的最新研究。我们强调了成骨细胞和破骨细胞分化中翻译后修饰的失调。我们还强调了翻译后修饰在骨质疏松症发展中的作用,以阐明骨质疏松症的潜在分子基础。然后,我们指出了将翻译后修饰作为治疗靶点的转化潜力。本综述将加深我们对翻译后修饰与骨质疏松症之间关系的理解,并确定临床治疗的新靶点以及未来的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a5/11959162/9a1acb634a5f/MCO2-6-e70159-g004.jpg

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