Abstract：
Stabilization of bone structure and function involves multiple cell-to-cell and molecular interactions, in which the regulatory functions of post-translational modifications such as ubiquitination and deubiquitination shouldn\'t be underestimated. As the largest family of deubiquitinating enzymes, the ubiquitin-specific proteases (USPs) participate in the development of bone homeostasis and bone-related diseases through multiple classical osteogenic and osteolytic signaling pathways, such as BMP/TGF-β pathway, NF-κB/p65 pathway, EGFR-MAPK pathway and Wnt/β-catenin pathway. Meanwhile, USPs may also broadly regulate regulate hormone expression level, cell proliferation and differentiation, and may further influence bone homeostasis from gene fusion and nuclear translocation of transcription factors. The number of patients with bone-related diseases is currently enormous, making exploration of their pathogenesis and targeted therapy a hot topic. Pathological increases in the levels of inflammatory mediators such as IL-1β and TNF-α lead to inflammatory bone diseases such as osteoarthritis, rheumatoid arthritis and periodontitis. While impaired body metabolism greatly increases the probability of osteoporosis. Abnormal physiological activity of bone-associated cells results in a variety of bone tumors. The regulatory role of USPs in bone-related disease has received particular attention from academics in recent studies. In this review, we focuse on the roles and mechanisms of USPs in bone homeostasis and bone-related diseases, with the expectation of informing targeted therapies in the clinic.
摘要：
骨骼结构和功能的稳定涉及多种细胞间和分子间的相互作用，其中翻译后修饰的调节功能如泛素化和去泛素化不可低估。作为最大的去泛素化酶家族，泛素特异性蛋白酶（USPs）通过多个经典的成骨和溶骨信号通路参与骨稳态和骨相关疾病的发展，如BMP/TGF-β途径，NF-κB/p65通路,EGFR-MAPK通路和Wnt/β-catenin通路。同时,USP还可以广泛调节激素表达水平，细胞增殖和分化，并可能进一步通过基因融合和转录因子的核易位影响骨稳态。目前骨相关疾病患者数量巨大,使探索其发病机制和靶向治疗成为热门话题。炎症介质如IL-1β和TNF-α水平的病理增加导致炎症性骨病如骨关节炎,类风湿性关节炎和牙周炎。而受损的身体代谢大大增加了骨质疏松症的可能性。骨相关细胞的异常生理活性导致多种骨肿瘤。在最近的研究中，USP在骨相关疾病中的调节作用受到了学术界的特别关注。在这次审查中,我们关注USP在骨稳态和骨相关疾病中的作用和机制，期望在临床上告知有针对性的治疗方法。
