TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling
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DOI：
10.1101/gad.13.8.1015
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发表时间：
1999-04-15
影响因子：
10.5
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Lomaga, MA;Yeh, WC;Mak, TW
骨吸收和重塑是一个复杂的控制，生理过程，需要破骨细胞的功能。破骨细胞的分化和活化过程涉及由肿瘤坏死因子（TNF）超家族成员骨保护素配体（OPGL）及其同源受体RANK诱导的信号。细胞内信号转导的分子机制仍有待阐明。在这里，我们报告说，小鼠肿瘤坏死因子受体相关因子6（TRAF 6）的缺陷是骨硬化症的骨重建和牙齿萌出的缺陷，由于破骨细胞功能受损。使用体外测定，我们证明TRAF 6不仅在IL-1和CD 40信号传导中至关重要，而且令人惊讶地在LPS信号传导中也至关重要。此外，与TRAF 2和TRAF 3一样，TRAF 6对围产期和产后生存至关重要。这些发现确立了TRAF 6在围产期和出生后存活、骨代谢、LPS和细胞因子信号传导中出乎意料的多样和关键作用。
Bone resorption and remodeling is an intricately controlled, physiological process that requires the function of osteoclasts. The processes governing both the differentiation and activation of osteoclasts involve signals induced by osteoprotegerin ligand (OPGL), a member of tumor necrosis factor (TNF) superfamily, and its cognate receptor RANK. The molecular mechanisms of the intracellular signal transduction remain to be elucidated. Here we report that mice deficient in TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function. Using in vitro assays, we demonstrate that TRAF6 is crucial not only in IL-1 and CD40 signaling but also, surprisingly, in LPS signaling. Furthermore, like TRAF2 and TRAF3, TRAF6 is essential for perinatal and postnatal survival. These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling.