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中华临床医师杂志(电子版) ›› 2022, Vol. 16 ›› Issue (03) : 274 -279. doi: 10.3877/cma.j.issn.1674-0785.2022.03.015

综述

TNF-α在绝经后骨质疏松症中的研究进展
蔡莉萍1, 燕琪慧1, 郭蔚莹1,()   
  1. 1. 130000 长春,吉林大学第一医院内分泌代谢科
  • 收稿日期:2021-07-06 出版日期:2022-03-15
  • 通信作者: 郭蔚莹

Progress in research of TNF-α in postmenopausal osteoporosis

Liping Cai1, Qihui Yan1, Weiying Guo1,()   

  1. 1. Department of Endocrinology and Metabolism, the First Hospital of Jilin University, Changchun 130000, China
  • Received:2021-07-06 Published:2022-03-15
  • Corresponding author: Weiying Guo
引用本文:

蔡莉萍, 燕琪慧, 郭蔚莹. TNF-α在绝经后骨质疏松症中的研究进展[J]. 中华临床医师杂志(电子版), 2022, 16(03): 274-279.

Liping Cai, Qihui Yan, Weiying Guo. Progress in research of TNF-α in postmenopausal osteoporosis[J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(03): 274-279.

肿瘤坏死因子-α(TNF-α)作为一种有效的促炎细胞因子,可刺激免疫细胞活化,促进炎症因子分泌,打破钙磷平衡,介导破骨细胞和成骨细胞的分化,通过多种途径调节骨代谢,参与绝经后骨质疏松症的发生发展,有望成为治疗绝经后骨质疏松症的药物靶点。本文分析TNF-α在绝经后骨质疏松症中的作用,以期为绝经后骨质疏松症的治疗提供新的方法。

Tumor necrosis factor α (TNF-α), as an effective pro-inflammatory cytokine, can stimulate the activation of immune cells, promote the secretion of inflammatory factors, break the balance of calcium and phosphorus metabolism, mediate the differentiation of osteoclasts and osteoblasts, regulate bone metabolism through various ways, and participate in the occurrence and development of postmenopausal osteoporosis, which is expected to be a drug target for the treatment of postmenopausal osteoporosis. This article analyzes the role of TNF-α in postmenopausal osteoporosis and provides a new method for the treatment of postmenopausal osteoporosis.

图1 破骨细胞成熟过程。造血干细胞在M-CSF刺激下分化为破骨细胞前体,破骨细胞前体在RANKL的影响下沿着朝向破骨细胞表型的轨迹继续前进,最终分化为具有活性的成熟的多核破骨细胞,在此过程中,OPG与RANKL结合阻止其与RANK缔合,从而降低了破骨细胞分化和骨吸收的速率 注:c-Fms为巨噬细胞集落刺激因子受体;M-CSF为巨噬细胞集落刺激因子;RANKL为核因子κB受体活化因子配体;OPG为骨保护素;RANK为核因子кB受体活化因子
图2 TNF-α调控破骨细胞分化途径 注:TNF-α为肿瘤坏死因子-α;RANKL为核因子κB受体活化因子配体;RANK为核因子κB受体活化因子;OPG为骨保护素;TNFR为肿瘤坏死因子受体;TRAF2为肿瘤坏死因子受体相关因子2;TRAF5为肿瘤坏死因子受体相关因子5;MAPK为丝裂原活化蛋白激酶;NF-κB为核因子κB;AP-1为激活蛋白1;PI3K为磷脂酰肌醇3-激酶;AKT为蛋白激酶B;P2X7 receptor为一种嘌呤受体;JNK位c-Jun N末端激酶;Semaphorin3D为信号素(Sema)家族成员之一,一种分泌型蛋白
图3 TNF-α调控成骨细胞分化途径 注:Wnt/β-catenin为Wnt配体/β-连环蛋白;semaphorin 3B为信号素家族成员之一,一种分泌型蛋白;ERK为细胞外信号调节激酶;JNK为c-Jun N末端激酶;P2Y2 receptor为一种嘌呤受体;SOX5为性别决定区Y框蛋白5;KLF4为Krüpple样因子4;smad1/5/8为细胞内信号传导蛋白;MAPK为丝裂原活化蛋白激酶;NF-κB为核因子κB;SATB2为富含AT序列的特异性结合蛋白2;Runx2为Runt相关转录因子2;BSP为骨唾液蛋白;EphB4为促红细胞生成肝细胞激酶(Eph)之一,介导细胞通信
图4 TNF-α介导免疫反应调节骨代谢 注:TNF-α为肿瘤坏死因子-α;RANKL为核因子κB受体活化因子配体;PTH为甲状旁腺激素;IL-12为白介素12;IL-17为白介素17;IL-18为白介素-18;POMP为绝经后骨质疏松症
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