Departments of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Departments of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Bone. 2022 Jun;159:116353. doi: 10.1016/j.bone.2022.116353. Epub 2022 Feb 16.
Since the receptor activator of nuclear factor-kappa B ligand (RANKL), its cognate receptor activator of nuclear factor-kappa B (RANK), and the decoy receptor osteoprotegerin (OPG) were discovered, a number of studies have uncovered the crucial role of the RANKL-RANK-OPG pathway in controlling the key aspect of bone homeostasis, the immune system, inflammation, cancer, and other systems under pathophysiological condition. These findings have expanded the understanding of the multifunctional biology of the RANKL-RANK-OPG pathway and led to the development of therapeutic potential targeting this pathway. The successful development and application of anti-RANKL antibody in treating diseases causing bone loss validates the utility of therapeutic approaches based on the modulation of this pathway. Moreover, recent studies have demonstrated the involvement of the RANKL-RANK pathway in osteoblast differentiation and bone formation, shedding light on the RANKL-RANK dual signaling in coupling bone resorption and bone formation. In this review, we will summarize the current understanding of the RANKL-RANK-OPG system in the context of the bone and the immune system as well as the impact of this pathway in disease conditions, including cancer development and metastasis.
自从核因子-κ B 配体受体激活剂（RANKL）、其同源受体核因子-κ B 受体激活剂（RANK）和诱饵受体护骨素（OPG）被发现以来，许多研究揭示了 RANKL-RANK-OPG 通路在控制骨稳态、免疫系统、炎症、癌症和其他系统的关键方面的关键作用在病理生理条件下。这些发现扩展了对 RANKL-RANK-OPG 通路多功能生物学的理解，并导致了针对该通路的治疗潜力的发展。抗 RANKL 抗体在治疗导致骨质流失的疾病中的成功开发和应用验证了基于该通路调节的治疗方法的实用性。此外，最近的研究表明 RANKL-RANK 途径参与成骨细胞分化和骨形成，揭示了 RANKL-RANK 双重信号在耦联骨吸收和骨形成中的作用。在这篇综述中，我们将总结 RANKL-RANK-OPG 系统在骨骼和免疫系统中的当前认识，以及该通路在疾病状况下的影响，包括癌症的发展和转移。
