肿瘤坏死因子α对骨组织细胞的调节  

Regulation of bone tissue cells by tumor necrosis factor-alpha

作　　者：王鑫[1] 吾布力卡斯木·米吉提 黄金勇 谢增如[1] Wang Xin;Wubulikasimu·Mijiti;Huang Jinyong;Xie Zengru(Department of Orthopedics and Trauma,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011)

机构地区：[1]新疆医科大学第一附属医院创伤骨科,新疆维吾尔自治区乌鲁木齐市830011

出　　处：《中国组织工程研究》2024年第21期3400-3406,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(82260409),项目负责人:谢增如;新疆维吾尔自治区科学技术厅重点项目(2021D01D19),项目负责人:谢增如;自治区研究生实践创新项目(XJ2023G165),项目负责人:王鑫。

摘　　要：背景:肿瘤坏死因子α是一种作用广泛的炎性细胞因子,在机体的免疫炎症反应中起重要作用。目前的研究认为,肿瘤坏死因子α对多种骨组织细胞具有显著的生物学效应。目的:总结肿瘤坏死因子α在成骨及破骨细胞中的表达及作用途径,以进一步阐明肿瘤坏死因子α对骨组织细胞的调控作用。方法:检索截至2023年3月的PubMed及中国知网数据库中的相关文献,中文检索词包括“肿瘤坏死因子α,成骨细胞,破骨细胞,骨细胞,骨祖细胞”;英文检索词包括“TNF-α,osteoblast,osteoclast,osteocyte,osteoprogenitor cell”,并根据研究需要确立相应的标准,对最终所得文献进行筛选,最终纳入77篇文献进行综述。结果与结论:①肿瘤坏死因子α参与调控了骨祖细胞的募集、增殖与分化,但在特定环境下导致骨祖细胞剥离及死亡。同时通过分泌酶类直接或间接参与骨质吸收。②肿瘤坏死因子α能够通过激活破骨系细胞中相关信号通路,提高环境中炎性因子水平,或在特定环境下直接诱导破骨细胞生成。③肿瘤坏死因子α可通过激活核转录因子κB信号通路,抑制RUNX2和Osterix等转录因子的表达从而抑制成骨分化并诱导成骨细胞的凋亡和坏死性凋亡。④肿瘤坏死因子α通过激活骨细胞中核转录因子κB信号通路,诱导RANKL、SOST及DKK1等细胞因子抑制成骨促进破骨,同时增强骨细胞的凋亡,以及凋亡骨组织周围的骨吸收。⑤综合而言,肿瘤坏死因子α在骨组织中的效应以抑制成骨、促进破骨为主,肿瘤坏死因子α在骨组织细胞中实现生物效应通常依赖于肿瘤坏死因子受体及核转录因子κB信号通路的激活。⑥未来的研究中肿瘤坏死因子α与骨组织周围其他组织细胞类型的交互以及在骨免疫调控中的作用仍值得关注。BACKGROUND:Tumor necrosis factor-αis a broadly acting inflammatory cytokine that plays an important role in the immune inflammatory response of the body.The current study concluded that tumor necrosis factor-αhas significant biological effects on a variety of bone tissue cells.OBJECTIVE:To summarize the expression and action pathways of tumor necrosis factor-αin osteoblastic and osteoclastic cells to further elucidate the regulatory role of tumor necrosis factor-αon bone tissue cells.METHODS:PubMed and CNKI were searched until March 2023,and the Chinese search terms included“tumor necrosis factorα,osteoblast,osteoclast,osteoclast,osteoprogenitor”;the English search terms included“TNF-α,osteoblast,osteoclast,osteocyte,osteoprogenitor cell”.The corresponding criteria were established according to the research needs,and the final literature was screened.Finally,77 articles were included for review.RESULTS AND CONCLUSION:(1)Tumor necrosis factor-αis participating in regulating the recruitment,appreciation,and differentiation of osteoprogenitor cells,but leads to osteoprogenitor cell stripping and death under specific environments.It also participates in bone resorption directly or indirectly through secreted enzymes.(2)Tumor necrosis factor-αcan increase the level of inflammatory factors in the environment by activating relevant signaling pathways in osteoclast lineage cells or directly induce the generation of osteoclasts in specific environments.(3)Tumor necrosis factor-αcan inhibit osteogenic differentiation by activating nuclear factor-κB signaling pathway,inhibiting the expression of transcription factors such as RUNX2 and Osterix,and inducing apoptosis and necrotizing apoptosis in osteoblasts.(4)Tumor necrosis factor-αinhibits osteogenesis and promotes osteoclastogenesis by activating the nuclear factor-κB signaling pathway in osteocytes and inducing cytokines such as RANKL,SOST,and DKK1,while enhancing apoptosis of the osteocytes,as well as bone resorption around the apoptotic bone tissue.(

关 键 词：肿瘤坏死因子Α 成骨细胞 破骨细胞 骨细胞 骨祖细胞 骨组织 细胞因子 信号通路 骨吸收 凋亡 

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