摘要骨骼是一个动态组织,在生物的整个生命周期中不断地进行构建、吸收、重建,核因子(nuclear factor,NF)κB受体活化因子(receptor activator of NF-κB,RANK)/NF-κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)/护骨素(osteoprotegerin,OPG)系统是调控这一过程的关键系统.RANK/RANKL/OPG属于肿瘤坏死因子及其受体超家族,三者通过调控破骨细胞的分化和活化来影响骨吸收和重建的过程.另外,免疫细胞也参与和调节RANK/RANKL的表达和分泌,而免疫细胞本身亦受到该系统的影响,因此,RANK/RANKL/OPG系统成为骨和免疫之间的重要关联.RANK/RANKL/OPG系统的失衡与多种骨代谢性疾病及免疫系统疾病引发的继发性骨病密切相关,该系统的发现为研究相关疾病的病理机制和治疗方法提供了基础.由此建立的抗RANKL疗法已经开始应用于临床试验和研究.此文对RANK/RANKL/OPG系统、系统相关疾病以及抗RANKL治疗的进展做一综述.

abstractsBone is a dynamic tissue, which is renewed continuously by modeling, resorption and remodeling in the life span. The receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand (RANKL)/osteoprotegerin(OPG)system is the key regulator of this process. The RANK/RANKL/OPG triad belongs to the tumor necrosis factor or tumor necrosis factor receptor superfamily. They control bone resorption and remodeling via regulation of the osteoclasts' differentiation and activation. As the expression of RANK and RANKL is regulated by immunocytes, while the immunocytes themselves are also affected by the RANKL/RANK signaling, the RANK/RANKL/OPG system becomes a crucial bridge between bone and immune system. The imbalance of RANK/RANKL/OPG system is associated with multiple bone metabolism diseases and secondary bone diseases of immune system disorders. The discovery of this system leads to a great advance in researches of the disease pathophysiology and the therapies. The anti-RANKL therapy has been under investigation in a series of clinical trials. This review summarizes the research progress in RANK/RANKL/OPG system and its associated diseases and the anti-RANKL therapy.