Institute of Molecular Biotechnology of the Austrian, Academy of Sciences, Vienna, Austria.
Adv Exp Med Biol. 2009;647:130-45. doi: 10.1007/978-0-387-89520-8_9.
Bone-related diseases, such as osteoporosis or rheumatoid arthritis, affect hundreds of millions of people worldwide and pose a tremendous burden to health care. By deepening our understanding of the molecular mechanisms of bone metabolism and bone turnover, it became possible over the past years to devise new and promising strategies for treating such diseases. In particular, three molecules, the receptor activator of NF-kappaB(RANK), its ligand RANKL and the decoy receptor of RANKL, osteoprotegerin (OPG), attracted the attention of scientists and pharmaceutical companies alike. Genetic experiments evolving around these molecules established their pivotal role as central regulators of osteoclast function. RANK-RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also fine-tunes bone homeostasis both in normal physiology and disease. Consequently, novel drugs specifically targeting RANK-RANKL and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various ailments associated with bone loss, such as arthritis, cancer metastases, or osteoporosis.
骨骼相关疾病，如骨质疏松症或类风湿性关节炎，影响着全球数以亿计的人群，给医疗保健带来了巨大的负担。近年来，通过深入了解骨骼代谢和骨转换的分子机制，为治疗这类疾病设计了新的、有前景的策略成为可能。特别是有三种分子，核因子 κB 受体激活物（RANK）、其配体 RANKL 和 RANKL 的诱饵受体骨保护素（OPG），引起了科学家和制药公司的关注。围绕这些分子进行的遗传实验确立了它们作为破骨细胞功能中央调节剂的关键作用。RANK-RANKL 信号不仅激活了破骨细胞发育所需的各种下游信号通路，而且与其他信号通路的串扰也精细地调节了正常生理和疾病状态下的骨稳态。因此，专门针对破骨细胞中 RANK-RANKL 及其信号通路的新型药物有望彻底改变与骨丢失相关的各种疾病的治疗，如关节炎、癌症转移或骨质疏松症。
