骨硬化蛋白：一个治疗骨质疏松的新靶点

Sclerostin--an potential therapeutic target for osteoporosis

高骨量疾病骨硬化症（sclerosteosis）和Van Buchem病由SOST基因表达缺失导致.由于SOST基因突变导致骨硬化蛋白不能表达或功能缺陷,可造成该病患者的过度骨形成,其作用机制与抑制Wnt信号转导通路相关.骨硬化蛋白通过与该通路共受体LRP5/6结合来阻断Wnt通路,进而对成骨细胞分化及矿化起抑制作用.由于骨硬化蛋白在抑制骨形成起关键作用且仅在骨组织表达,其单克隆抗体可用于治疗低骨量疾病如骨质疏松.

The loss of the SOST gene product sclerostin leads to sclerosteosis and Van Buchem disease characterized by high bone mass. Excessive bone formation in sclerosteosis and Van Buchem disease may result from the absence of or insensitivity to sclerostin,which inhibits Wnt pathway. Sclerostin antagonizes ca-onical Wnt signaling by binding to Wnt coreceptors, low-density lipoprotein receptor-related protein 5 and 6. Thus,it inhibits Wnt-induced osteoblast differentiation and bone mineralization. The essential role of sclerostin in inhibiting bone formation and its restricted expression pattern in bone make its monoclonal antibody an potential therapeutic target to treat patients with bone disease characterized by low bone mass,such as osteoporosis.