Baud'huin M, Lamoureux F, Duplomb L, Rédini F, Heymann D
Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique Universités, F-44035, Nantes, France.
Cell Mol Life Sci. 2007 Sep;64(18):2334-50. doi: 10.1007/s00018-007-7104-0.
1997 saw the identification of a novel set of proteins within the tumor necrosis factor (TNF)/TNF receptor families that are required for the control of bone remodeling. Therefore, these receptors, receptor activator of nuclear factor kappa B (RANK), osteoprotegerin (OPG) and their ligand RANK ligand (RANKL) became the critical molecular triad controlling osteoclastogenesis and pathophysiologic bone remodeling. However, the establishment of the corresponding knock-out and transgenic mice revealed unexpected results, most particularly, the involvement of these factors in the vascular system and immunity. Thus, the OPG/RANK/RANKL molecular triad appears to be associated with vascular calcifications and plays a pivotal function in the development of the immune system through dendritic cells. OPG/RANK/RANKL thus constitute a molecular bridge spanning bone metabolism, vascular biology and immunity. This review summarizes recent knowledge of OPG/RANK/RANKL interactions and activities as well as the current evidence for their participation in osteoimmunology and vascular diseases. In fine, the targeting of the OPG/RANK/RANKL axis as novel therapeutic approaches will be discussed.
1997年，人们在肿瘤坏死因子（TNF）/TNF受体家族中发现了一组新的蛋白质，它们对于控制骨重塑至关重要。因此，这些受体，即核因子κB受体激活剂（RANK）、骨保护素（OPG）及其配体RANK配体（RANKL），成为了控制破骨细胞生成和病理生理性骨重塑的关键分子三联体。然而，相应基因敲除和转基因小鼠的建立却揭示了意想不到的结果，最显著的是这些因子在血管系统和免疫中的作用。因此，OPG/RANK/RANKL分子三联体似乎与血管钙化有关，并通过树突状细胞在免疫系统发育中发挥关键作用。OPG/RANK/RANKL因此构成了一座跨越骨代谢、血管生物学和免疫的分子桥梁。本综述总结了关于OPG/RANK/RANKL相互作用和活性的最新知识，以及它们参与骨免疫学和血管疾病的当前证据。最后，将讨论针对OPG/RANK/RANKL轴作为新型治疗方法的研究。
