Novel insights into the role of ubiquitination in osteoarthritis

Yuzhe Lin; Shide Jiang; Jingyue Su; Wenqing Xie; Masoud Rahmati; Yuxiang Wu; Shengwu Yang; Qin Ru; Yusheng Li; Zhenhan Deng

doi:10.1016/j.intimp.2024.112026

Novel insights into the role of ubiquitination in osteoarthritis

Int Immunopharmacol. 2024 Apr 6:132:112026. doi: 10.1016/j.intimp.2024.112026. Online ahead of print.

Authors

Yuzhe Lin¹, Shide Jiang², Jingyue Su³, Wenqing Xie⁴, Masoud Rahmati⁵, Yuxiang Wu⁶, Shengwu Yang³, Qin Ru⁷, Yusheng Li⁸, Zhenhan Deng⁹

Affiliations

¹ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China; Xiangya School of Medicine, Central South University, Changsha, China.
² Department of Orthopedics, The Central Hospital of Yongzhou, Yongzhou, 425000, China.
³ Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran; Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran.
⁶ Department of Health and Physical Education, Jianghan University, Wuhan 430056, China.
⁷ Xiangya School of Medicine, Central South University, Changsha, China; Department of Health and Physical Education, Jianghan University, Wuhan 430056, China. Electronic address: ruqin@jhun.edu.
⁸ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: liyusheng@csu.edu.cn.
⁹ Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address: dengzhenhan@wmu.edu.cn.

PMID: 38583240
DOI: 10.1016/j.intimp.2024.112026

Abstract

Ubiquitination (Ub) and deubiquitination are crucial post-translational modifications (PTMs) that precisely regulate protein degradation. Under the catalysis of a cascade of E1-E2-E3 ubiquitin enzymes, ubiquitination extensively regulates protein degradation exerting direct impact on various cellular processes, while deubiquitination opposes the effect of ubiquitination and prevents proteins from degradation. Notably, such dynamic modifications have been widely investigated to be implicated in cell cycle, transcriptional regulation, apoptosis and so on. Therefore, dysregulation of ubiquitination and deubiquitination could lead to certain diseases through abnormal protein accumulation and clearance. Increasing researches have revealed that the dysregulation of catalytic regulators of ubiquitination and deubiquitination triggers imbalance of cartilage homeostasis that promotes osteoarthritis (OA) progression. Hence, it is now believed that targeting on Ub enzymes and deubiquitinating enzymes (DUBs) would provide potential therapeutic pathways. In the following sections, we will summarize the biological role of Ub enzymes and DUBs in the development and progression of OA by focusing on the updating researches, with the aim of deepening our understanding of the underlying molecular mechanism of OA pathogenesis concerning ubiquitination and deubiquitination, so as to explore novel potential therapeutic targets of OA treatment.

Keywords: Cartilage degradation; Deubiquitination; Osteoarthritis; Pathogenesis; Ubiquitination.

Publication types

Review