破骨细胞功能调控与骨吸收抑制剂

Osteoclast function regulation and bone resorption inhibitors

骨质疏松症是骨强度下降导致骨折危险性升高的一种骨骼疾病。破骨细胞是人体唯一的骨吸收细胞,与骨质疏松症的发生密切相关,近年来对于破骨细胞与骨吸收有了较深入的研究,并研发了多种抗骨吸收的靶向药物。本文结合国内外研究简述破骨细胞与核因子κB受体活化因子配体(receptor activator for nuclear factor-κB ligand,RANKL)/核因子κB受体活化因子(receptor activator for nuclear factor-κB,RANK)/骨保护素(orthopantomography,OPG)信号通路、Wnt/β-catenin信号通路、细胞因子、组织蛋白酶K和Src激酶之间的关系,并对新型骨吸收抑制剂RANKL的单克隆抗体Denosumab、Wnt信号传导拮抗剂Romosozumab、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)拮抗剂、白细胞介素-6 (interleukin-6,IL-6)受体拮抗剂Tocilizumab、组织蛋白酶K抑制剂Odanacatib、Src激酶抑制剂Saracatinib等进行综述,为骨质疏松症的防治提供相关依据。

Osteoporosis is a skeletal disorder in which the bone strength decreases leading to an increased risk of fracture. Osteoclasts are the only human bone resorption cells, which are closely related to the occurrence of osteoporosis. In recent years, they have conducted in-depth studies on osteoclasts and bone resorption, and have developed a variety of targeted drugs for resorption. We briefly described the research of the relationship between osteoclasts and receptor activator for nuclear factor-KB ligand/receptor activator for nuclear factor-KB/orthopantomography （ RANKL/ RANK/OPG） signaling pathway, Wnt/β-catenin signaling pathway, cytokines, cathepsin K and Src kinase, the new bone absorption of monoclonal anti RANKL antagonistic agent Denosumab, Wnt signaling antagonist Romosozumab, tumor necrosis factor-α （TNF-α） antagonist, interleukin-6 （IL-6） receptor antagonist Tocilizumab, cathepsin K inhibitor Odanacatib and Src kinase inhibitor Saracatinib, to provide the relevant evidence for the prevention and treatment of osteoporosis.