RANK-RANKL信号通路在骨质疏松症中的研究进展

Research Progress of RANK-RANKL Signaling Pathway in Osteoporosis

摘要: 骨质疏松症(osteoporosis, OP)是一种以骨量减少、骨组织微结构破坏、骨脆性增加伴有骨强度下降，极易发生骨折为特征的全身性骨代谢疾病，是老年人群及绝经后女性骨折的主要诱因。RANKL/RANK/OPG信号通路包含骨保护素(OPG)、细胞核因子kB受体活化因子(RANK)配体(RANKL)，该通路通过OPG与RANKL结合来抑制RANKL/RANK介导的破骨细胞信号传导，调控破骨细胞分化与功能活性，参与骨重建过程，从而发挥抗骨质疏松作用。近年来，针对该通路的深入研究不仅加深了我们对骨质疏松发病机制的理解，更催生了极具突破性的靶向治疗策略。本文旨在系统综述RANK-RANKL通路在骨质疏松症中的分子机制，详细探讨其在骨质疏松症发病中的作用，以及多种药物对该通路的调控作用，为研究更加安全、有效的抗骨质疏松药物提供新的作用靶点和理论依据。

Abstract: Osteoporosis (OP) is a systemic metabolic bone disease characterized by reduced bone mass, deterioration of bone tissue microstructure, increased bone fragility accompanied by decreased bone strength, and a high susceptibility to fractures. It serves as a primary contributing factor to fractures in elderly populations and postmenopausal women. The RANKL/RANK/OPG signaling pathway comprises osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK), and its ligand RANKL. This pathway inhibits RANKL/RANK-mediated osteoclast signaling by binding OPG to RANKL, thereby regulating osteoclast differentiation and functional activity, participating in bone remodeling processes, and exerting anti-osteoporotic effects. In recent years, in-depth research on this pathway has not only enhanced our understanding of osteoporosis pathogenesis but also led to groundbreaking targeted therapeutic strategies. This article systematically reviews the molecular mechanisms of the RANK-RANKL pathway in osteoporosis, thoroughly examines its role in the disease’s onset, and discusses the regulatory effects of various drugs on this pathway, aiming to provide novel therapeutic targets and theoretical foundations for developing safer and more effective anti-osteoporosis medications.