Does TNF have anti-osteoclastogenic actions?
Does TNF have anti-osteoclastogenic actions?
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DOI：
10.1196/annals.1346.056
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Iqbal, Jameel
中科院分区：
文献类型：
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作者：
Iqbal, Jameel
肿瘤坏死因子 (TNF) 是一种促吸收剂，会导致骨降解。已经提出了几种作用机制来解释这些效应： TNF 直接抑制成骨细胞分化； TNF 通过诱导基质细胞增加 RANKL 和巨噬细胞集落刺激因子 (M-CSF) 的表达并减少骨保护素 (OPG) 的表达来增强破骨细胞的形成； TNF与RANK下游通路协同作用，直接增加破骨细胞分化。所有这些作用总而言之表明 TNF 在过度表达或注射后会显着诱导骨质减少。然而，用 TNF 观察到的骨质减少明显比 OPG(-/-) 动物中观察到的骨质减少轻，这促使人们重新评估 TNF 作用的现有范例。通过检查 TNF 对 RANKL 诱导的破骨细胞形成和标记物表达的影响，检验了 TNF 直接增强破骨细胞分化的假设。数据显示TNF降低RANKL诱导的破骨细胞标记物、TRAP和组织蛋白酶K的表达。此外，添加10-60ng/mL TNF未能显着增加RANKL诱导的破骨细胞分化。相反，数据表明 TNF 的促破骨作用是通过增加可用破骨细胞前体（巨噬细胞）数量来介导的。
Tumor necrosis factor (TNF) is a pro-resorption agent that leads to bone degradation. Several mechanisms of action have been proposed to account for these effects: TNF directly inhibits osteoblast differentiation; TNF augments osteoclast formation by inducing stromal cells to increase expression of RANKL and macrophage colony-stimulating factor (M-CSF) and decrease that of osteoprotegerin (OPG); and TNF serves to synergize with pathways downstream of RANK to directly increase osteoclast differentiation. All of these actions in sum suggest that TNF dramatically induces osteopenia upon overexpression or injection. However, that the osteopenia seen with TNF is significantly milder than that seen in OPG(-/-) animals prompted a reevaluation of existing paradigms on TNF action. The hypothesis that TNF directly enhances osteoclast differentiation was tested by examining the effects of TNF on RANKL-induced osteoclast formation and marker expression. The data show that TNF decreased RANKL-induced expression of the osteoclast markers, TRAP and cathepsin K. Furthermore, the addition of 10-60 ng/mL TNF failed to significantly increase RANKL-induced osteoclast differentiation. Instead, data are presented to suggest that the pro-osteoclastogenic actions of TNF are mediated through increases in the number of available osteoclast precursors (macrophages).