Department of Physical and Biocoordination Chemistry, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.
Molecules. 2021 Oct 27;26(21):6491. doi: 10.3390/molecules26216491.
Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women's osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RANK/RANKL signaling provides the opportunity to design novel therapeutic agents to inhibit bone loss, based on the anti-RANKL treatment and inhibition of its interaction with the RANK receptor. The new generation of both anti- and mesoprogestins that inhibit the NF-κB-cyclin D1 axis and blocks the binding of RANKL to RANK can be considered as a potential source of new RANK receptor ligands with anti-RANKL function, which may provide a new perspective into osteoporosis treatment itself as well as limit the osteoporosis rise during breast cancer metastasis to the bone.
核因子 κB 受体激活剂（RANK）及其配体（RANKL）在骨骼代谢和免疫系统中发挥着关键作用。研究表明，RANK/RANKL 复合物在乳腺上皮细胞的形成中也起着关键作用。女性激素雌二醇和孕酮通过与 RANK 密切控制 RANKL 的作用。绝经后这些性激素在血液中的浓度会导致 RANK/RANKL 信号的增加，这是女性骨质疏松症的主要原因，其特征是骨矿化改变。了解激素与 RANK/RANKL 信号之间的生化关系为设计基于抗 RANKL 治疗和抑制其与 RANK 受体相互作用的新型治疗药物提供了机会，以抑制骨质流失。新一代既能抑制 NF-κB-细胞周期蛋白 D1 轴又能阻止 RANKL 与 RANK 结合的抗孕激素和中孕激素可被视为具有抗 RANKL 功能的新型 RANK 受体配体的潜在来源，这不仅为骨质疏松症的治疗提供了新视角，还限制了乳腺癌转移至骨骼时骨质疏松症的发生。
