Minireview: the OPG/RANKL/RANK system.
Minireview: the OPG/RANKL/RANK system.
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DOI：
10.1210/endo.142.12.8536
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发表时间：
2001-12
期刊：
影响因子：
4.8
通讯作者：
S. Khosla
中科院分区：
文献类型：
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作者：
S. Khosla
OPG/RANKL/RANK系统作为破骨细胞生成的主要最终介质的鉴定代表了骨生物学的重大进展。它结束了长期以来对前成骨细胞/基质细胞产生的特定因子的研究，这些细胞对破骨细胞的发育既必要又足够。OPG作为属于TNF受体超家族的可溶性诱饵受体的最初克隆和表征是最终导致该系统解开的第一步。此后不久，被OPG阻断的分子，最初称为OPG-配体/破骨细胞分化因子（ODF），随后称为RANKL，被鉴定为破骨细胞生成的关键介质，在前成骨细胞/基质细胞上表达的膜结合形式以及可溶性形式。RANKL，反过来，被证明结合其受体，RANK，破骨细胞谱系细胞。这些分子表达改变的小鼠极端骨骼表型（骨质疏松症与石骨症）的发现证明了这些因素在调节骨代谢中发挥的决定性作用。在过去的几年里，工作重点是确定调节该系统的因素、RANKL/RANK途径中涉及的信号机制，以及最后，代谢性骨病中该系统的潜在改变，从极其常见的（即绝经后骨质疏松症）到罕见的（即家族性膨胀性骨质溶解）。
The identification of the OPG/RANKL/RANK system as the dominant, final mediator of osteoclastogenesis represents a major advance in bone biology. It ended a long-standing search for the specific factor produced by preosteoblastic/stromal cells that was both necessary and sufficient for osteoclast development. The initial cloning and characterization of OPG as a soluble, decoy receptor belonging to the TNF receptor superfamily was the first step that eventually led to an unraveling of this system. Soon thereafter, the molecule blocked by OPG, initially called OPG-ligand/osteoclast differentiating factor (ODF) and subsequently RANKL, was identified as the key mediator of osteoclastogenesis in both a membrane-bound form expressed on preosteoblastic/stromal cells as well as a soluble form. RANKL, in turn, was shown to bind its receptor, RANK, on osteoclast lineage cells. The decisive role played by these factors in regulating bone metabolism was demonstrated by the findings of extremes of skeletal phenotypes (osteoporosis vs. osteopetrosis) in mice with altered expression of these molecules. Over the past several years, work has focused on identifying the factors regulating this system, the signaling mechanisms involved in the RANKL/RANK pathway, and finally, potential alterations in this system in metabolic bone disorders, from the extremely common (i.e. postmenopausal osteoporosis) to the rare (i.e. familial expansile osteolysis).