Department of Orthopaedics and Traumatology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, China.
Department of Orthopaedics, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Front Immunol. 2023 Jun 9;14:1217466. doi: 10.3389/fimmu.2023.1217466. eCollection 2023.
Osteoarthritis is non-inflammatory degenerative joint arthritis, which exacerbates disability in elder persons. The molecular mechanisms of osteoarthritis are elusive. Ubiquitination, one type of post-translational modifications, has been demonstrated to accelerate or ameliorate the development and progression of osteoarthritis targeting specific proteins for ubiquitination and determining protein stability and localization. Ubiquitination process can be reversed by a class of deubiquitinases deubiquitination. In this review, we summarize the current knowledge regarding the multifaceted role of E3 ubiquitin ligases in the pathogenesis of osteoarthritis. We also describe the molecular insight of deubiquitinases into osteoarthritis processes. Moreover, we highlight the multiple compounds that target E3 ubiquitin ligases or deubiquitinases to influence osteoarthritis progression. We discuss the challenge and future perspectives modulation of E3 ubiquitin ligases and deubiquitinases expression for enhancement of the therapeutic efficacy in osteoarthritis patients. We conclude that modulating ubiquitination and deubiquitination could alleviate the osteoarthritis pathogenesis to achieve the better treatment outcomes in osteoarthritis patients.
骨关节炎是非炎症性退行性关节病，会加剧老年人的残疾。骨关节炎的分子机制尚不清楚。泛素化，一种翻译后修饰类型，已被证明可以通过针对特定蛋白质的泛素化和确定蛋白质稳定性和定位来加速或改善骨关节炎的发展和进展。泛素化过程可以通过一类去泛素化酶来逆转，即去泛素化。在这篇综述中，我们总结了 E3 泛素连接酶在骨关节炎发病机制中的多方面作用的最新知识。我们还描述了去泛素化酶对骨关节炎过程的分子认识。此外，我们强调了多种针对 E3 泛素连接酶或去泛素化酶的化合物，以影响骨关节炎的进展。我们讨论了挑战和未来展望，即调节 E3 泛素连接酶和去泛素化酶的表达，以增强骨关节炎患者的治疗效果。我们的结论是，调节泛素化和去泛素化可以减轻骨关节炎的发病机制，从而在骨关节炎患者中实现更好的治疗效果。
