Regulatory Mechanisms of RANKL Presentation to Osteoclast Precursors
Regulatory Mechanisms of RANKL Presentation to Osteoclast Precursors
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DOI：
10.1007/s11914-014-0189-0
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发表时间：
2014-03-01
影响因子：
4.3
通讯作者：
Suzuki, Hiroshi
中科院分区：
文献类型：
--
作者：
Honma, Masashi;Ikebuchi, Yuki;Suzuki, Hiroshi
由于破骨细胞的过度活化与各种骨质减少性疾病有关，因此了解破骨细胞形成的分子调控机制非常重要。核因子κ B受体激活因子（RANKL）是破骨细胞生成的主要参与者。最近的研究结果表明，骨细胞是破骨细胞前体RANKL的主要供应者。也有人认为，骨细胞死亡上调了骨微损伤区域中与凋亡骨细胞相邻的存活骨细胞中的RANKL/骨保护素（OPG）比率，从而促进了局部破骨细胞的形成。事实上，存活的骨细胞可以通过与骨细胞树枝状突起处的破骨细胞前体直接相互作用来提供RANKL。此外，OPG紧密调节骨细胞中RANKL细胞表面呈递，这有助于抑制RANKL信号传导以及OPG的诱饵受体功能。相比之下，RANKL在成骨细胞中的生理作用尚未阐明，尽管在骨细胞和成骨细胞中观察到类似的调节机制。
It is important to understand the molecular mechanisms regulating osteoclast formation, as excess activation of osteoclasts is associated with various osteopenic disorders. Receptor activator of nuclear factor kappa B (RANKL) is a central player in osteoclastogenesis. Recent findings suggest that osteocytes are the major supplier of RANKL to osteoclast precursors. It has also been suggested that osteocyte cell death upregulates the RANKL/osteoprotegerin (OPG) ratio in viable osteocytes adjacent to apoptotic osteocytes in areas of bone microdamage, thus, contributing to localized osteoclast formation. Indeed, viable osteocytes can provide RANKL through direct interactions with osteoclast precursors at osteocyte dendritic processes. In addition, OPG tightly regulates RANKL cell surface presentation in osteocytes, which contributes to the inhibition of RANKL signaling, as well as the decoy receptor function of OPG. By contrast, the physiological role of RANKL in osteoblasts is yet to be clarified, although similar mechanisms of regulation are observed in both osteocytes and osteoblasts.