Deciphering the role of RANK/RANKL/OPG in skeletal muscle

RANK/RANKL/OPG--核因子κB受体-激活因子（RANK）、核因子κB受体-激活因子配体（RANKL）和骨保护素（OPG）通路的发现是骨生物学和疾病领域最重要的进展之一。RANK/RANKL/OPG形成调节破骨细胞分化和功能的关键细胞因子系统。RANKL由成骨细胞表达，而其受体RANK在前成骨细胞上表达。RANK/RANKL相互作用诱导多核成熟破骨细胞的形成，最终导致骨吸收。然而，第三个主角OPG也由成骨细胞产生，并对前骨细胞分化产生抑制作用。OPG通过与RANKL结合，抑制RANKL/RANK相互作用和随后的破骨细胞生成。OPG基因敲除的小鼠是类人猿，这一事实证明了OPG的生理重要性。OPG也可作为肿瘤坏死因子相关凋亡诱导配体的诱饵受体，通过阻断RANK/RANKL相互作用的促凋亡作用增加细胞存活。因此，OPG是一种非常有效的抗再吸收和抗凋亡剂。然而，我们最近的出版物在上午。J. Pathol.（2015）令人信服地表明，OPG-Fc完全恢复了mdx小鼠快缩趾长伸肌的功能，并显著改善了慢缩比目鱼肌和膈肌的功能，表明OPG不仅是骨的保护剂，也是骨骼肌的保护剂。

The discovery of RANK/RANKL/OPG the receptor-activator of nuclear factor κB (RANK), the receptor-activator of nuclear factor κB ligand (RANKL), and the osteoprotegerin (OPG) pathway has been among the most important advances in bone biology and disease. RANK/RANKL/OPG form a key cytokine system for regulating osteoclast differentiation and function. RANKL is expressed by osteoblasts while RANK, its receptor, is expressed on pre-osteoclastic cells. The RANK/RANKL interaction induces the formation of multinucleated mature osteoclasts, ultimately causing bone resorption. However, the third protagonist, OPG, is also produced by osteoblasts and exerts an inhibitory effect on pre-osteoclastic differentiation. OPG, by binding to RANKL, inhibits the RANKL/RANK interaction and the subsequent osteoclastogenesis. The fact that OPG-null mice are osteoporotic is testimony to the physiological importance of OPG. OPG also serves as a decoy receptor for the tumour necrosis factor-related apoptosis-inducing ligand and increases cell survival by blocking the pro-apoptotic effects of the RANK/RANKL interaction. OPG is thus a very efficient anti-resorptive and anti-apoptotic agent. However, our recent publication in Am. J. Pathol. (2015) convincingly showed that OPG-Fc completely restores the function of fast-twitch extensor digitorum longus muscles and significantly improves the function of slow-twitch soleus and diaphragm muscles in mdx mice, indicating that OPG is not only a protector of bone but also skeletal muscles.