Yamamoto Masahiro
Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
Clin Calcium. 2014 Nov;24(11):1643-50.
Sclerostin, a glycoprotein encoded by SOST gene and secreted from osteocyte, is known as an antagonist for bone formation induced in canonical Wnt/β-catenin signaling pathway by inhibiting receptor complex formation through binding to LDL receptor-related protein 5/6 (LRP 5/6) . From clinical symptoms observed in the patients with a loss-of-function mutation in LRP 6, disorder of that signal transduction pathway is considered as one of candidate molecular mechanism for the simultaneous occurrence of diabetes mellitus and osteoporosis. The serum sclerostin levels of diabetic patients as well as non-diabetic subjects are significantly and positively correlated with bone mineral density, which is the strongest determinant factor especially for diabetic patients. In addition, sclerostin concentrations are associated with prevalent vertebral fractures independent of bone mineral density as well as bone turnover, suggesting that elevated sclerostin levels reflect poor bone quality.
硬化蛋白是一种由SOST基因编码并由骨细胞分泌的糖蛋白,它通过与低密度脂蛋白受体相关蛋白5/6(LRP 5/6)结合来抑制受体复合物的形成,从而作为经典Wnt/β-连环蛋白信号通路中诱导骨形成的拮抗剂。从LRP 6功能丧失突变患者观察到的临床症状来看,该信号转导通路的紊乱被认为是糖尿病和骨质疏松症同时发生的候选分子机制之一。糖尿病患者以及非糖尿病受试者的血清硬化蛋白水平与骨密度显著正相关,骨密度是尤其对于糖尿病患者而言最强的决定因素。此外,硬化蛋白浓度与椎体骨折的发生相关,且独立于骨密度以及骨转换,这表明硬化蛋白水平升高反映了骨质量较差。