Ohnaka Keizo
Kyushyu University, Graduate School of Medical Sciences, Department of Geriatric Medicine.
Clin Calcium. 2006 Nov;16(11):1812-6.
Wnt signaling plays an important role not only in development and morphogenesis of embryos but in pathogenesis of various disorders including cancers. Analyses of the mutations in LDL receptor-related protein 5 (LRP5), a Wnt co-receptor, revealed that the Wnt signaling pathway is important for bone formation. Glucocorticoids suppress the canonical Wnt signaling pathway by such mechanisms as the enhancement the expression of dickkopf-1 (Dkk-1) and secreted frizzled-related protein 1 (sFRP1), and activation of the glycogen synthase kinase-3beta (GSK-3beta) activity. The inhibition of the canonical Wnt signal by glucocorticoid may be involved in the pathogenesis of glucocorticoid-induced osteoporosis.
Wnt信号通路不仅在胚胎发育和形态发生中起重要作用，而且在包括癌症在内的各种疾病的发病机制中也发挥着重要作用。对Wnt共受体低密度脂蛋白受体相关蛋白5（LRP5）突变的分析表明，Wnt信号通路对骨形成很重要。糖皮质激素通过增强Dickkopf-1（Dkk-1）和分泌型卷曲相关蛋白1（sFRP1）的表达以及激活糖原合酶激酶-3β（GSK-3β）活性等机制抑制经典Wnt信号通路。糖皮质激素对经典Wnt信号的抑制可能参与了糖皮质激素诱导的骨质疏松症的发病机制。
