Zeng Ruiyin, Xiong Yuan, Lin Ze, Panayi Adriana C, Sun Yun, Cao Faqi, Liu Guohui
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China.
Stem Cells Int. 2022 Sep 27;2022:6948367. doi: 10.1155/2022/6948367. eCollection 2022.
The ubiquitination-proteasome system (UPS) is crucial in regulating a variety of cellular processes including proliferation, differentiation, and survival. Ubiquitin protein ligase E3 is the most critical molecule in the UPS system. Dysregulation of the UPS system is associated with many conditions. Over the past few decades, there have been an increasing number of studies focusing on the UPS system and how it affects bone metabolism. Multiple E3 ubiquitin ligases have been found to mediate osteogenesis or osteolysis through a variety of pathways. In this review, we describe the mechanisms of UPS, especially E3 ubiquitin ligases on bone metabolism. To date, many E3 ubiquitin ligases have been found to regulate osteogenesis or osteoclast differentiation. We review the classification of these E3 enzymes and the mechanisms that influence upstream and downstream molecules and transduction pathways. Finally, this paper reviews the discovery of the relevant UPS inhibitors, drug molecules, and noncoding RNAs so far and prospects the future research and treatment.
泛素化-蛋白酶体系统（UPS）在调节包括增殖、分化和存活在内的多种细胞过程中至关重要。泛素蛋白连接酶E3是UPS系统中最关键的分子。UPS系统的失调与许多病症相关。在过去几十年中，越来越多的研究聚焦于UPS系统及其对骨代谢的影响。已发现多种E3泛素连接酶通过多种途径介导成骨或骨吸收。在本综述中，我们描述了UPS的机制，尤其是E3泛素连接酶对骨代谢的影响。迄今为止，已发现许多E3泛素连接酶调节成骨或破骨细胞分化。我们综述了这些E3酶的分类以及影响上游和下游分子及转导途径的机制。最后，本文综述了迄今为止相关UPS抑制剂、药物分子和非编码RNA的发现，并对未来的研究和治疗进行了展望。
