沉默信息调节因子6是骨组织再生修复的潜在作用靶点  

Research advances on silence information regulator 6 as a potential therapeutic target for bone regeneration and repair

作　　者：潘闻政 何勇[1] 黄悦[1] PAN Wenzheng;HE Yong;HUANG Yue(Department of Orthopedics,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China)

机构地区：[1]浙江大学医学院附属邵逸夫医院骨科,浙江杭州310016

出　　处：《浙江大学学报（医学版）》2024年第4期427-433,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省基础公益研究计划(LGF21H060005);浙江省卫生健康科技计划(2022KY826)。

摘　　要：创伤、感染、肿瘤或全身性疾病等因素引起的节段性骨缺损和骨折不愈合具有成骨范围局限、骨骼愈合周期长等特点。骨组织再生代谢调节因子可加速骨组织修复和高效重建骨缺损区。沉默信息调节因子6(SIRT6)作为一种去乙酰化酶和核苷酸转移酶,广泛参与成骨细胞和破骨细胞等骨细胞的分化、凋亡、代谢和炎症反应的调节,是骨代谢调节的重要因子。SIRT6通过与B淋巴细胞诱导成熟蛋白1形成复合体,并下调核因子κB通路表达,促进雌激素受体α-Fas配体轴信号表达,以抑制破骨细胞生成和成熟分化,从而阻碍骨吸收,导致骨组织骨量增加。另外,SIRT6能通过激活Akt-mTOR途径调节骨髓间充质干细胞自噬水平和成骨能力,并抑制成骨细胞内糖酵解和活性氧生成,通过CREB/CCN1/COX2途径和骨形态发生蛋白信号通路促进成骨细胞分化增加骨的形成,加速骨组织骨再生修复。本文综述了SIRT6参与骨再生病理生理机制的研究进展,揭示其可能作为骨组织修复潜在治疗靶点的意义。Segmental bone defects and nonunion of fractures caused by trauma,infection,tumor or systemic diseases with limited osteogenesis and prolonged bone healing cycles are challenging issues in orthopedic clinical practice.Therefore,identifying regulatory factors for bone tissue regeneration and metabolism is crucial for accelerating bone repair and reconstructing defective areas.Silence information regulator 6(SIRT6),functioning as a deacetylase and nucleotide transferase,is extensively involved in the regulation of differentiation,apoptosis,metabolism,and inflammation in bone cells including osteoblasts and osteoclasts,and is considered to be an important factor in regulating bone metabolism.SIRT6 forms a complex with B lymphocyte-induced maturation protein 1(Blimp1),down-regulates the expression of the nuclear factorκB(NF-κB)pathway,and promotes the expression of the ERα-FasL axis signal to inhibit osteoclast formation and maturation differentiation,thereby hindering bone resorption and increasing bone mass.In addition,SIRT6 activates the Akt-mTOR pathway to regulate the autophagy level and osteogenesis of bone marrow mesenchymal stem cells,inhibits glycolysis and reactive oxygen production in osteoblasts,promotes osteoblast differentiation through the CREB/CCN1/COX2 pathway and the bone morphogenetic protein(BMP)signaling pathway,enhances bone formation,and accelerates bone regeneration and repair of skeletal tissue.This article provides an overview of the research progress on SIRT6 in the pathophysiology of bone regeneration,revealing its potential as a novel therapeutic target for bone tissue repair to alleviate the progression of skeletal pathological diseases.

关 键 词：沉默信息调节因子6 骨代谢 骨再生 修复 综述 

分 类 号：R641[医药卫生—外科学]