Silva I, Branco Jaime C
Serviço de Reumatologia, Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, EPE, Portugal.
Acta Reumatol Port. 2011 Jul-Sep;36(3):209-18.
The discovery of the receptor activator of nuclear factor-kB (RANK)/RANK Ligand (RANKL)/osteoprotegerin (OPG) pathway contributed to the understanding of how bone formation and resorption were processed and regulated. RANKL and OPG are members of the tumor necrosis factor (TNF) and TNF receptor (TNFr) superfamilies, respectively, and binding to receptor activator of NF-kB (RANK) not only regulate osteoclast formation, activation and survival in normal bone modeling and remode-ling, but also in several other pathologic conditions characterized by increased bone turnover. There is accumulating evidence of the potential role of OPG and RANKL in other tissues. Looking beyond the RANK/RANKL/OPG axis, Wingless (Wnt) pathway emerged as the osteoblast differentiation way, and also as a bone mass regulator. Researchers have been discovering new molecules and cytokines interactions. Altogether, data suggest that RANK/RANKL/OPG system could be targeted as a new treatment strategy in bone conditions. FREEDOM is the more recently published clinical trial about a RANKL-specific recombinant fully human monoclonal antibody (denosumab). OPG is also a potential innovative therapeutic option to be investigated.
核因子-κB受体激活剂（RANK）/RANK配体（RANKL）/骨保护素（OPG）通路的发现有助于理解骨形成和吸收是如何进行和调节的。RANKL和OPG分别是肿瘤坏死因子（TNF）和TNF受体（TNFr）超家族的成员，与NF-κB受体激活剂（RANK）结合不仅在正常骨建模和重塑中调节破骨细胞的形成、激活和存活，而且在其他几种以骨转换增加为特征的病理状况中也起调节作用。越来越多的证据表明OPG和RANKL在其他组织中具有潜在作用。除了RANK/RANKL/OPG轴，无翅型（Wnt）通路已成为成骨细胞分化途径以及骨量调节因子。研究人员一直在发现新的分子和细胞因子相互作用。总体而言，数据表明RANK/RANKL/OPG系统可作为骨疾病的一种新治疗策略。FREEDOM是最近发表的一项关于RANKL特异性重组全人单克隆抗体（地诺单抗）的临床试验。OPG也是一种有待研究的潜在创新治疗选择。
