叉头框转录因子O1信号通路与骨代谢  

Forkhead box transcription factor O1 signaling pathway in bone metabolism

作　　者：赵济宇 王少伟[2] Zhao Jiyu;Wang Shaowei(Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;Department of Orthopedics,The Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学,山西省太原市030001 [2]山西医科大学第二医院骨科,山西省太原市030001

出　　处：《中国组织工程研究》2025年第9期1923-1930,共8页Chinese Journal of Tissue Engineering Research

摘　　要：背景:在骨骼中,各种内源性或者外源性刺激会引起骨代谢失衡,导致骨量和骨强度的变化,进而引起骨关节炎、骨质疏松症等一系列骨相关疾病。在这个过程中,叉头框转录因子O1(Forkhead box transcription factor O1,FoxO1)起到了重要作用,FoxO1可以通过调节氧化应激、细胞增殖、分化和凋亡来调控骨代谢。目的:文章以FoxO1为中心,通过总结其上下游的调节机制,为未来治疗骨相关疾病提供新的思路。方法:以“FoxO1,骨”为检索词在中国知网和万方医学数据库进行检索,以“FoxO1,Bone,Skeleton”为检索词在PubMed和Web of Science数据库进行检索,排除陈旧、重复、质量较差以及不相关的文献,最终纳入56篇文献进行综述分析。结果与结论:①FoxO1通过增加Runt相关转录因子2、碱性磷酸酶和骨钙素的表达,促进骨髓间充质干细胞向成骨细胞分化,通过抑制过氧化物酶体增殖激活受体γ,将骨髓间充质干细胞由成脂分化向成骨分化转化,从而增加骨形成。此外,FoxO1还可以通过增加成骨细胞的数量来影响骨形成。②抑制骨髓单核-巨噬细胞中的FoxO1可以导致巨噬细胞集落刺激因子、核因子κB受体激活剂配体以及活化T细胞核因子1表达减少,促进破骨细胞表达更多的FoxO1,从而抑制破骨细胞分化。此外,直接激活FoxO1也可以抑制破骨细胞分化并减弱破骨细胞的活性。③增加软骨细胞内的FoxO1水平可以起到调节软骨细胞稳态、保护软骨细胞免受氧化应激损伤、促进自噬相关基因的表达和软骨细胞分泌蛋白多糖4的作用。④文章详细介绍了FoxO1在不同骨细胞中调节的分子机制,更加全面、深入地阐述了FoxO1在治疗骨相关疾病中的关键作用,为治疗骨关节炎、骨质疏松症及骨折愈合延迟等多种骨相关疾病提供新的思路。BACKGROUND:In the skeleton,various endogenous or exogenous stimuli cause imbalance in bone metabolism,leading to changes in bone mass and bone strength,which in turn cause a series of bone-related diseases such as osteoarthritis and osteoporosis.In this process,Forkhead box transcription factor O1(FoxO1)plays an important role,and FoxO1 can regulate bone metabolism by regulating oxidative stress,cell proliferation,differentiation and apoptosis.OBJECTIVE:This paper focuses on FoxO1,and by summarizing its upstream and downstream regulatory mechanisms,it provides new ideas for the future treatment of bone-related diseases.METHODS:The search terms“FoxO1,Bone”were used for literature retrieval in CNKI and WanFang Databases,and the search terms“FoxO1,Bone,Skeleton”were used in PubMed and Web of Science databases.The old,repetitive,poor quality and irrelevant papers were excluded,and 56 papers were finally included for review and analysis.RESULTS AND CONCLUSION:(1)FoxO1 promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts by increasing the expression of runt-related transcription factor 2,alkaline phosphatase and osteocalcin,and transforms bone marrow mesenchymal stem cells from lipogenic differentiation to osteogenic differentiation by inhibiting peroxisome proliferator-activated receptorγ,thereby increasing bone formation.In addition,FoxO1 may also affect bone formation by increasing the number of osteoblasts.(2)Inhibition of FoxO1 in bone marrow mononuclear macrophages can reduce the expression of macrophage colony-stimulating factor,receptor activator of nuclear factor-κB ligand and nuclear factor of activated T cells 1,promote the expression of FoxO1 in osteoclasts,and thus inhibit osteoclast differentiation.In addition,direct activation of FoxO1 also inhibits osteoclast differentiation and weakens osteoclast activity.(3)Upregulation of FoxO1 in chondrocytes can regulate chondrocyte homeostasis,protect chondrocytes from oxidative stress,and promote the expression of autophag

关 键 词：FOXO1 骨代谢 氧化应激 成骨细胞 破骨细胞 软骨细胞 骨关节炎 骨质疏松症 骨折愈合 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364