Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis
Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis
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DOI：
10.1084/jem.20050978
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发表时间：
2005-09-05
影响因子：
15.3
通讯作者：
Choi, Y
中科院分区：
文献类型：
--
作者：
Kim, N;Kadono, Y;Choi, Y
破骨细胞来源于髓系细胞，它们的分化受到各种骨促因子的支持，包括肿瘤坏死因子（TNF）家族成员TNF相关活化诱导细胞因子（TRANCE）。TRANCE或其受体（核因子κ B受体激活剂（RANK））的基因缺失导致严重骨硬化小鼠的骨骼中无破骨细胞。TNF受体相关因子（TRAF）6是RANK的关键信号适配器，其缺乏导致类似的骨硬化症。因此，目前的范式认为TRANCE-RANK相互作用和随后通过TRAF 6的信号传导对于功能性破骨细胞的生成至关重要。令人惊讶的是，我们发现TRANCE-，RANK-或TRAF 6-null小鼠的造血前体细胞在体外可以成为破骨细胞，当它们在辅因子如TGF-β的存在下用TNF-α刺激时。我们提供了直接证据，反对目前的范式，TRANCE-RANK-TRAF 6途径是破骨细胞分化所必需的，并表明破骨细胞分化的替代途径的潜在存在。
Osteoclasts are derived from myeloid lineage cells, and their differentiation is supported by various osteotropic factors, including the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE). Genetic deletion of TRANCE or its receptor, receptor activator of nuclear factor kappa B (RANK), results in severely osteopetrotic mice with no osteoclasts in their bones. TNF receptor-associated factor (TRAF) 6 is a key signaling adaptor for RANK, and its deficiency leads to similar osteopetrosis. Hence, the current paradigm holds that TRANCE-RANK interaction and subsequent signaling via TRAF6 are essential for the generation of functional osteoclasts. Surprisingly, we show that hematopoietic precursors from TRANCE-, RANK-, or TRAF6-null mice can become osteoclasts in vitro when they are stimulated with TNF-alpha in the presence of cofactors such as TGF-beta. We provide direct evidence against the current paradigm that the TRANCE-RANK-TRAF6 pathway is essential for osteoclast differentiation and suggest the potential existence of alternative routes for osteoclast differentiation.