Inhibition of RANK/RANKL signal transduction pathway: A promising approach for osteoporosis treatment
Inhibition of RANK/RANKL signal transduction pathway: A promising approach for osteoporosis treatment
复制标题
抑制 RANK/RANKL 信号转导通路：骨质疏松症治疗的一种有前景的方法
DOI：
10.1016/j.mehy.2008.03.021
复制
发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Wu, Bu-Ling
中科院分区：
文献类型：
--
作者：
Bai, Yu-Di;Yang, Fu-Sheng;Wu, Bu-Ling
骨质疏松症是一种导致骨骼强度受损的骨骼疾病。它的特点是破骨细胞形成增加或骨吸收增强，导致脆性骨折的风险增加。它的患病率随着年龄的增长而增加。人口老龄化的到来表明，逐渐有更多的人会在老龄化人口中患上这种疾病。许多预防和治疗骨质疏松症的药物是通过抑制骨吸收来发挥作用的。然而，骨质疏松症的临床治疗效果有限。由于破骨细胞是体内唯一能够吸收骨的细胞，了解其生物学特性对于开发治疗骨质疏松症的新方法是必要的。近年来发现，核因子kappa B受体激活物(RANK)/RANKL/OPG系统是调节破骨细胞形成的重要信号转导途径。OPG与RANKL的结合抑制了RANKL与RANK的结合，进而阻止破骨细胞前体分化和融合形成成熟破骨细胞。因此，RANK/RANKL通路的抑制抑制了破骨细胞的形成、分化、激活和骨吸收。使用抗RANKL的单抗，如地诺舒单抗，可以高亲和力和特异性地与RANKL结合，阻断RANKL-RANK的相互作用，从而开发出一种潜在的临床抗吸收治疗方法。(C)2008爱思唯尔有限公司。保留所有权利。
Osteoporosis is a bone disease causing impaired bone strength. It is characterized by increased osteoclast formation or enhanced bone resorption, leading to an increased risk of fragility fractures. its prevalence increases with age. The advent of an aging population suggests that progressively more individuals will develop this disease in the aging population. A number of drugs for the prevention and treatment of osteoporosis act by inhibiting bone resorption. However, the effectiveness of osteoporosis treatment in clinical practice is limited. Since the osteoclast is the only cell in the body that is capable of resorbing bone, understanding its biology will be necessary for developing a new therapeutic approach for osteoporosis. Recently, it was discovered that the receptor activator of nuclear factor kappa B (RANK)/RANK Ligand (RANKL)/osteoprotegerin (OPG) system is an important signal transduction pathway that regulates osteoclast formation. The binding of OPG to RANKL inhibits the binding between RANKL and RANK; this, in turn, prevents osteoclast precursors from differentiating and fusing to form mature osteoclasts. Therefore, the inhibition of the RANK/RANKL pathway inhibits osteoclast formation, differentiation, activation, and bone resorption. A potential clinical antiresorptive therapy can be developed by using an anti-RANKL monoclonal antibody, such as denosumab, that binds to RANKL with high affinity and specificity and blocks RANKL-RANK interactions. (C) 2008 Elsevier Ltd. All rights reserved.