Riddle Ryan C
Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Research and Development Service, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.
Curr Opin Endocr Metab Res. 2023 Feb;28. doi: 10.1016/j.coemr.2022.100433.
Sclerostin, the product of the gene has primarily been studied for its profound impact on bone mass. By interacting with LRP5 and LRP6, the glycoprotein suppresses the propagation of Wnt signals to β-catenin and thereby suppresses new bone formation. In this review, we discuss emerging data which suggest that sclerostin also acts outside the skeleton to influence metabolism. In humans, serum sclerostin levels are associated with body mass index and indices of metabolic function. Likewise, genetic mouse models of gene deficiency indicate sclerostin influences adipocyte development and insulin signaling. These data raise the possibility that sclerostin neutralization may be effective at treating two epidemic conditions: osteoporosis and obesity.
硬化素是该基因的产物,主要因其对骨量的深远影响而受到研究。通过与低密度脂蛋白受体相关蛋白5(LRP5)和低密度脂蛋白受体相关蛋白6(LRP6)相互作用,这种糖蛋白抑制Wnt信号向β-连环蛋白的传导,从而抑制新骨形成。在本综述中,我们讨论了新出现的数据,这些数据表明硬化素也在骨骼外发挥作用以影响代谢。在人类中,血清硬化素水平与体重指数和代谢功能指标相关。同样,该基因缺陷的基因小鼠模型表明硬化素会影响脂肪细胞发育和胰岛素信号传导。这些数据增加了中和硬化素可能有效治疗两种流行病状的可能性:骨质疏松症和肥胖症。