Negative autoregulation of RANKL and c-Src signaling in osteoclasts
Negative autoregulation of RANKL and c-Src signaling in osteoclasts
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DOI：
10.1007/s00774-007-0751-2
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发表时间：
2007-06
影响因子：
3.3
通讯作者：
K. Yogo;N. Ishida-Kitagawa;T. Takeya
中科院分区：
文献类型：
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作者：
K. Yogo;N. Ishida-Kitagawa;T. Takeya
破骨细胞是多核巨细胞，负责骨基质降解。破骨细胞的分化和骨吸收过程的机制已在分子水平上进行了广泛的研究。特别是，核因子-κB配体（RANKL）信号级联的受体激活剂的发现为后续研究奠定了基础，以了解破骨细胞的各个方面。RANKL作为分化和骨吸收的必需因子，调节许多分子以协调破骨细胞的分化和功能。这些分子中的大多数已被证明在破骨细胞生成和/或骨吸收中发挥积极作用;然而，研究表明RANKL也可以诱导自身调节信号并调节其自身的信号级联反应。这种调节机制可能有助于防止破骨细胞的过度形成和活化，从而从整体上控制骨代谢。我们在c-Src中新发现了这种机制，并在RANKL诱导的破骨细胞生成的背景下讨论了其意义。
Osteoclasts are multinucleated giant cells that are responsible for bone matrix degradation. The mechanisms of differentiation and bone resorption processes in osteoclasts have been investigated extensively at the molecular level. In particular, the discovery of the receptor activator of the nuclear factor-κB ligand (RANKL) signaling cascade built the foundation for subsequent studies to understand the various aspects of osteoclasts. RANKL, as an essential factor for differentiation and bone resorption, regulates a number of molecules to orchestrate differentiation as well as the function of osteoclasts. Most of those molecules have been proven to play positive roles in osteoclastogenesis and/or bone resorption; however, studies showing that RANKL could also induce autoregulatory signals and modulate its own signaling cascades have been accumulating. Such a regulatory mechanism (s) may contribute to prevent the excess formation and activation of osteoclasts and thereby, to control bone metabolism as a whole. We newly identified such a mechanism in c-Src, and its significance is discussed in the context of RANKL-induced osteoclastogenesis.