泛素特异性蛋白酶调控骨重建的研究进展  

Research progress on ubiquitin-specific proteases in regulation of bone remodeling

作　　者：张国锐 伍颖颖[2] 熊毅 ZHANG Guorui;WU Yingying;XIONG Yi(State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&West China School of Stomatology,Sichuan University,Chengdu 610041,China;State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Oral Implantology,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China)

机构地区：[1]口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心四川大学华西口腔医学院,四川成都610041 [2]口腔疾病研究国家重点实验室国家口腔疾病临床医学研究中心四川大学华西口腔医院种植科,四川成都610041

出　　处：《口腔疾病防治》2022年第11期832-836,共5页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金项目(82001084)。

摘　　要：骨重建包含破骨细胞介导的骨吸收和成骨细胞介导的骨形成,生理状态下二者相互耦联维持骨稳态。越来越多的研究发现泛素蛋白酶途径在骨重建过程中扮演重要角色。泛素化的可逆性是由去泛素化酶实现的,其中,泛素特异性蛋白酶(ubiquitin-specific proteases,USPs)是数量最多的去泛素化酶。目前研究表明,泛素特异性蛋白酶可通过调节成骨细胞、破骨细胞的分化及功能,进而影响骨重建过程。本文总结了USPs调控骨重建的相关机制,包括USP4、USP7等通过调控Wnt/β-catenin等信号通路影响骨形成,圆柱瘤基因(cylindromatosis,CYLD)等通过核因子κB(nuclear factor-kappa B,NF-κB)等信号通路调控骨吸收。除了影响骨重建中的骨吸收与骨形成作用,USPs对骨的影响还体现在人牙周膜干细胞的成骨分化与种植体骨结合方面。未来的研究方向应寻找USPs对骨重建是否具有更多的调节作用,以及其调节作用的具体机制,为治疗骨骼疾病提供更多途径。Maintaining bone homeostasis relies on the balance between bone remodeling involving bone resorption by osteoclasts and bone formation by osteoblasts under physiological conditions.An increasing number of studies have shown that the ubiquitin-proteasome system plays an important role in bone remodeling.The ubiquitination process is reversible through the action of deubiquitinase(DUB),and ubiquitin-specific proteases(USPs)are the largest of the DUB families.This article summarizes the mechanisms by which USPs regulate bone homeostasis,including USP4 and USP7,by affecting bone formation through signaling pathways such as Wnt/β-catenin and cylindromatosis(CYLD)and regulating bone resorption through signaling pathways such as nuclear factor-kappa B(NF-κB).In addition to affecting bone resorption and bone formation during bone reconstruction,the effect of USPs on bone is also reflected in the osteogenic differentiation of human periodontal membrane stem cells and implant bone binding.Future research should determine whether USPs have a greater regulatory effect on bone reconstruction and the specific mechanism of their regulato ry effect to provide more approaches for the treatment of bone diseases.

关 键 词：骨重建 牙周炎 种植体骨结合 泛素化 泛素特异性蛋白酶 成骨细胞 破骨细胞 机制 WNT信号通路 核因子ΚB信号通路 

分 类 号：R78[医药卫生—口腔医学]