绝经后骨质疏松症TNF-α通过激活NF-κB促进RANKL诱导的破骨细胞形成

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英文篇名：Promotion of TNF-α on RANKL-induced Osteoclast Formation by Activating NF-κB in Postmenopausal Osteoporosis 作者：陈鹏 ; 李杨 ; 胡伟文 ; 李健 ; 何润泽 英文作者：Chen Peng;Li Yang;Hu Weiwen;Li Jian;He Runze;Xiangnan University Affiliated Hospital; 关键词：绝经后骨质疏松症 ; 肿瘤坏死因子-α(TNF-α) ; 核因子κB受体激活因子配体(RANKL) ; 核因子-κB(NF-κB) ; 破骨细胞 英文关键词：Postmenopausal osteoporosis;;Tumor necrosis factor-α(TNF-α);;Receptor activator for NF-κB ligand(RANKL);;Nuclear factor kappa-B(NF-κB);;Osteoclast 中文刊名：GXNB 英文刊名：Genomics and Applied Biology 机构：湘南学院附属医院; 出版日期：2019-02-25 出版单位：基因组学与应用生物学 年：2019 期：v.38 语种：中文; 页：GXNB201902071 页数：6 CN：02 ISSN：45-1369/Q 分类号：482-487

摘要

本研究检测了绝经后骨质疏松症妇女的肿瘤坏死因子-α(TNF-α)和雌激素水平,并探讨了TNF-α对破骨前体细胞RAW264.7中破骨细胞标志物核因子κB受体激活因子(nuclear factor kappa-B, RANK)、组织蛋白酶K (Cathepsin K, CTSK)和凝血酶受体激活肽(thrombin receptor activating peptide, TRAP)以及核因子-κB (NF-κB)亚基(p65)和NF-κB抑制蛋白(IκBα)的影响。研究结果表明,绝经后骨质疏松症患者的TNF-α水平显著升高,而雌二醇水平显著降低。核因子κB受体激活因子配体(receptor activator for NF-κBligand, RANKL)处理1周后,破骨前体细胞RAW264.7中破骨细胞标志物RANK、CTSK和TRAP的mRNA和蛋白高度表达。与RANKL对照组相比,TNF-α处理可上调RANK、CTSK和TRAP m RNA的表达。但是,仅TNF-α不能诱导培养的RAW264.7细胞分化为破骨细胞成。TNF-α以剂量依赖性方式诱导NF-κB亚基p65和IκBα磷酸化,而NF-κB抑制剂处理则有效降低了RANK和TRAP的表达。本研究结论表明,绝经后骨质疏松症中TNF-α通过激活NF-κB来促进RANKL诱导的破骨细胞形成。
        This study detected the levels of TNF-α and estrogen in postmenopausal women with osteoporosis and investigated the effect of TNF-α on the osteoclast markers(RANK, CTSK and TRAP), NF-κB subunit(p65) and NF-κB inhibitory protein(IκBα) in osteoclast precursor cell RAW264.7. The results showed that TNF-α level in postmenopausal osteoporosis patients was significantly elevated, while estradiol level was significantly reduced.After 1 week of RANKL treatment, the osteoclast markers, RANK, CTSK and TRAP m RNA and protein were highly expressed in osteoclast precursor cell RAW264.7. Compared with RANKL control group, TNF-α treatment could up-regulated the expression of RANK, CTSK and TRAP mRNA. However, only with TNF-α could not induce the differentiation of cultured RAW264.7 cells into osteoclasts. TNF-α induced NF-κB subunit(p65) and IκBα phosphorylation in a do se-dependent manner, whereas NF-κB inhibitor treatment effectively reduced the expression of RANK and TRAP. The conclusion of this study suggested that TNF-α could promote RANKL-induced osteoclast formation by activating NF-κB in postmenopausal osteoporosis.

引文

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