Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai 810000, P.R. China.
Qinghai Provincial People's Hospital, Department of Endocrinology, Xining, Qinghai 810000, P.R. China.
Int J Mol Med. 2024 Aug;54(2). doi: 10.3892/ijmm.2024.5392. Epub 2024 Jun 28.
The ubiquitin (Ub)‑proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including skeletal cell differentiation and bone homeostasis. The Ub ligase E3 promotes the transfer of Ub to the target protein, especially transcription factors, to regulate the proliferation, differentiation and survival of bone cells, as well as bone formation. In turn, the deubiquitinating enzyme removes Ub from modified substrate proteins to orchestrate bone remodeling. As a result of abnormal regulation of ubiquitination, bone cell differentiation exhibits disorder and then bone homeostasis is affected, consequently leading to osteoporosis. The present review discussed the role and mechanism of UPS in bone remodeling. However, the specific mechanism of UPS in the process of bone remodeling is still not fully understood and further research is required. The study of the mechanism of action of UPS can provide new ideas and methods for the prevention and treatment of osteoporosis. In addition, the most commonly used osteoporosis drugs that target ubiquitination processes in the clinic are discussed in the current review.
泛素(Ub)-蛋白酶体系统(UPS)在维持蛋白质内稳态和功能方面发挥着关键作用,可调节包括骨骼细胞分化和骨内稳态在内的各种细胞过程。Ub 连接酶 E3 促进 Ub 向靶蛋白(特别是转录因子)的转移,以调节骨细胞的增殖、分化和存活以及骨形成。反过来,去泛素化酶从修饰的底物蛋白上去除 Ub,以协调骨重塑。由于泛素化的异常调节,骨细胞分化表现出紊乱,随后骨内稳态受到影响,最终导致骨质疏松症。本综述讨论了 UPS 在骨重塑中的作用和机制。然而,UPS 在骨重塑过程中的具体机制尚不完全清楚,需要进一步研究。UPS 作用机制的研究可为骨质疏松症的预防和治疗提供新的思路和方法。此外,本综述还讨论了目前临床上针对泛素化过程的骨质疏松症最常用药物。