Wnt信号通路在糖尿病骨质疏松中的作用及中药干预的研究进展

Role of W nt signaling Pathway in Diabetic Osteoporosis and Traditional Chinese Medicine Intervention:A Review

糖尿病骨质疏松(DOP)是糖尿病引起的一种骨骼并发症,以骨密度降低、骨微结构改变、骨质脆性升高为主要特征。DOP的进程与高糖、胰岛素抵抗、氧化应激等机制关系密切。Wnt/β-连环蛋白(β-catenin)信号通路是介导糖尿病胰岛素抵抗和骨代谢平衡的重要机制,调控Wnt信号转导促进糖原合成酶激酶-3β(GSK-3β)磷酸化表达水平,可改善糖脂代谢。Wnt/β-catenin信号通路是调节骨细胞重塑的重要途径,不仅在成骨细胞和破骨细胞二者平衡中发挥重要调节作用,可以改善骨代谢平衡;并且调控Wnt通路还促进骨桥蛋白、骨钙素、Ⅰ型胶原蛋白的表达,改善骨增殖和成骨分化。近年来中医药在DOP的防治中的研究逐渐增多,中药干预Wnt通路转导改善DOP的探索取得了一定的进展。该文搜集国内外近10年来Wnt信号通路在糖代谢、骨代谢和DOP的研究,以及关于中药复方(经典方和其他)、单味中药、中药单体基于Wnt通路干预DOP的相关文献进行整理综述,以期为临床防治DOP新药的开发提供参考和方向。

Diabetic osteoporosis(DOP)is a kind of bone complication caused by diabetes,which is characterized by the decrease of bone mineral density,the change of bone microstructure and the increase of bone fragility.The process of DOP is closely related to high glucose,insulin resistance,oxidative stress and other mechanisms.The W nt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes.Regulation of W nt signal transduction promotes the expression of glycogen synthase kinase-3β(GSK-3β)phosphorylation and improves glucose and lipid metabolism. The W nt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling, which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis, but also promotes the expression of osteopontin, osteocalcin and type I collagen, and improves bone proliferation and osteogenic differentiation by regulating the W nt pathway. In recent years, the research of traditional Chinese medicine (TCM) in the prevention and treatment of DOP has gradually increased, and the exploration of TCM to interfere with the W nt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the W nt signaling pathway in glucose metabolism,bone metabolism and DOP worldwide in the past decade, as well as the related literature on the intervention of DOP by TCM compounds (classical and other compounds), single Chinese medicine and TCM monomers based on the W nt pathway, in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.