Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond.
Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond.
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DOI：
10.3389/fimmu.2014.00511
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发表时间：
2014
影响因子：
7.3
通讯作者：
Choi Y
中科院分区：
文献类型：
--
作者：
Walsh MC;Choi Y
细胞因子受体-细胞因子-诱饵受体三联体的发现和表征不仅在理解骨稳态生物学方面取得了巨大进展，而且还明确了骨与免疫之间存在的关键调节关系，导致骨免疫学的新兴领域的出现。RANKL-RANK-OPG是肿瘤坏死因子（TNF）和TNF受体超家族的成员，具有每个家族许多成员共有的信号传导特征。这些因子的发育调节和细胞类型特异性表达模式揭示了RANKL-RANK-OPG在骨稳态、器官发生、免疫耐受和癌症中的关键调节功能。针对骨质疏松症的RANKL-RANK-OPG靶向治疗药物的设计和开发工作已经取得成功，其他疾病的治疗工作也在进行中。在这篇综述中，我们将总结RANKL-RANK-OPG系统的基本生物学，将其细胞类型特异性功能与全系统发育和稳态机制联系起来，并强调该细胞因子组的新兴感兴趣领域。
Discovery and characterization of the cytokine receptor-cytokine-decoy receptor triad formed by receptor activator of nuclear factor kappa-B ligand (RANKL)–receptor activator of NF-κB (RANK)–osteoprotegerin (OPG) have led not only to immense advances in understanding the biology of bone homeostasis, but have also crystalized appreciation of the critical regulatory relationship that exists between bone and immunity, resulting in the emergence of the burgeoning field of osteoimmunology. RANKL–RANK–OPG are members of the tumor necrosis factor (TNF) and TNF receptor superfamilies, and share signaling characteristics common to many members of each. Developmentally regulated and cell-type specific expression patterns of each of these factors have revealed key regulatory functions for RANKL–RANK–OPG in bone homeostasis, organogenesis, immune tolerance, and cancer. Successful efforts at designing and developing therapeutic agents targeting RANKL–RANK–OPG have been undertaken for osteoporosis, and additional efforts are underway for other conditions. In this review, we will summarize the basic biology of the RANKL–RANK–OPG system, relate its cell-type specific functions to system-wide mechanisms of development and homeostasis, and highlight emerging areas of interest for this cytokine group.