TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway.
TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway.
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DOI：
10.3892/mmr.2018.8698
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发表时间：
2018-05
影响因子：
3.4
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Luo G;Li F;Li X;Wang ZG;Zhang B
尽管肿瘤坏死因子-α在炎性骨溶解的发病机制中起重要作用，但其影响破骨细胞募集和分化的确切机制仍不清楚。为探讨肿瘤坏死因子-α影响破骨细胞分化的机制，以小鼠骨髓来源的巨噬细胞为破骨细胞前体细胞，用巨噬细胞集落刺激因子和核因子受体激活剂B配体(NF-κB Ligand，RANKL)诱导破骨细胞生成，并与肿瘤坏死因子-α联合作用4d。然后，用BAY 11-7082抑制NF-κB。结果表明，单独应用肿瘤坏死因子-α不能诱导骨髓基质细胞发生破骨细胞分化。而肿瘤坏死因子-α联合RANKL可显著刺激破骨细胞分化，并正向调节破骨细胞标志物的表达。最后，用BAY11-7082处理的骨髓基质细胞阻止了单独用肿瘤坏死因子-α或RANKL处理的骨髓基质细胞的成熟破骨细胞的形成，以及破骨细胞标志基因的上调。因此，尽管肿瘤坏死因子-α不能单独诱导破骨细胞生成，但它确实与RANKL一起诱导破骨细胞分化，而NF-κB通路可能在这一过程中发挥重要作用。
Although tumor necrosis factor alpha (TNF-α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF-α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF-α influences osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony-stimulating factor and receptor activator of nuclear factor (NF)-κB ligand (RANKL) with or without TNF-α for 4 days. Then, NF-κB was inhibited using the inhibitor, BAY 11–7082. The results indicated that treatment with TNF-α alone did not induce osteoclastogenesis of BMMs. However, TNF-α in combination with RANKL dramatically stimulated the differentiation of osteoclasts and positively regulated the expression of mRNA markers of osteoclasts. Finally, treatment of BMMs with BAY 11–7082 prevented the formation of mature osteoclasts by BMMs treated with TNF-α only or with RANKL, as well as the upregulation of osteoclast marker genes. Therefore, although TNF-α does not induce osteoclastogenesis alone, it does work with RANKL to induce osteoclastic differentiation, and the NF-κB pathway may serve an important role in this process.
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DOI：
10.2174/1568010054022015
发表时间：
2005-06-05
期刊：
Current Drug Targets - Inflammation and Allergy
影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
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2015-01-01
期刊：
NF-KAPPA B: METHODS AND PROTOCOLS
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作者：
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通讯作者：
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DOI：
10.1007/978-1-4939-0669-7_10
发表时间：
2014-01-01
期刊：
TNF SUPERFAMILY: METHODS AND PROTOCOLS
影响因子：
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作者：
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影响因子：
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作者：
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