Nagy Vanja, Penninger Josef M
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
Gerontology. 2015;61(6):534-42. doi: 10.1159/000371845. Epub 2015 Feb 14.
Receptor activator of nuclear factor x03BA;B (RANK) and its ligand (RANKL) have originally been described for their key roles in bone metabolism and the immune system. Subsequently, it has been shown that the RANKL-RANK system is critical in the formation of mammary epithelia in lactating females and the thermoregulation of the central nervous system. RANKL and RANK are under the tight control of the female sex hormones estradiol and progesterone. A reduction of the circulating female sex hormones leading to an increase in RANKL-RANK signaling is the leading cause of osteoporosis in postmenopausal women. Denosumab, a human monoclonal anti-RANKL antibody, has been approved for the treatment of postmenopausal osteoporosis, where it is showing great promise. In addition, RANKL-RANK signaling also plays a critical role in other bone pathologies, bone metastasis or hormone-driven breast cancer. This review will highlight some of the functions of RANKL-RANK in bone turnover, the immune system and brain with a focus on the regulatory role of the female sex hormones.
核因子κB受体激活剂（RANK）及其配体（RANKL）最初因其在骨代谢和免疫系统中的关键作用而被描述。随后，研究表明RANKL-RANK系统在哺乳期雌性动物乳腺上皮的形成以及中枢神经系统的体温调节中至关重要。RANKL和RANK受到雌性激素雌二醇和孕酮的严格调控。循环中的雌性激素减少导致RANKL-RANK信号传导增加是绝经后女性骨质疏松症的主要原因。地诺单抗，一种人源化抗RANKL单克隆抗体，已被批准用于治疗绝经后骨质疏松症，且显示出巨大的前景。此外，RANKL-RANK信号传导在其他骨病、骨转移或激素驱动的乳腺癌中也起着关键作用。本综述将重点介绍RANKL-RANK在骨转换、免疫系统和大脑中的一些功能，重点关注雌性激素的调节作用。
