摘要
大量研究显示Wnt/β-catenin信号通路在肾性骨病发生发展中具有重要作用。本文从生理、病理两个层面综述了Wnt/β-catenin信号通路在肾骨调控中的作用。在生理状态下,Wnt/β-catenin信号通路不仅具有调节肾形成祖细胞自我更新与分化,进而形成足量的肾单位的作用,而且可以促进多能间充质干细胞分化成成骨细胞系,抑制其向软骨以及脂肪细胞系分化的同时抑制成骨细胞凋亡,延长其生命,促进骨形成,还可以通过调节OPG的表达抑制破骨细胞分化和骨吸收。当肾脏受损后,在SOST、DKK1、Vitamin D/VDR、FGF23/α-Klotho、PTH/PTH1R、TGF-β/BMPs等诸多因素直接或间接影响下,一方面骨细胞中Wnt/β-catenin信号表达异常,影响正常的骨形成与骨吸收,引起骨稳态失衡进而发生骨病,另一方面肾脏中Wnt/β-catenin信号的异常表达或加速或修复自身损伤,并进一步影响骨稳态。
A number of researches have revealed the important roles of wnt/β-catenin signaling pathway in the pathogenesis of renal osteopathy. This reviewsummarizes howwnt/β-catenin signaling pathway regulates kidney and bone in pathological and physiological status. In the physiological state,wnt/β-catenin signaling pathway not only regulates self-renewal and differentiation of nephrogenesis nephronprogenitor cells to generate sufficient nephrons,but also regulates the homeostasis of bone： promoting pluripotent mesenchymal stem cells to differentiate into osteoblast lineage rather than differentiate into cartilage or adipocyte lineage,inhibiting osteoblast apoptosis to promote bone formation,and regulating the production of OPG to inhibit osteoclast-mediated bone resorption. After the kidney damage,under the directly or indirectly influence of many factors（such as： SOST,DKK1,Vitamin D/VDR,FGF23/α-Klotho,PTH/PTH1 R,TGF-β/BMPs）,abnormal signal expression of wnt/β-catenin pathway in bone affects normal bone formation and bone resorption,leading to unbalancing bone disease. In addition,abnormal wnt/β-catenin signaling pathway in the kidney may aggravate or repair the self-damage,which in turns affects bone homeostasis.
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2016年第12期1618-1622,1636,共6页
Chinese Journal of Osteoporosis
基金
科技部创新人才推进计划重点领域"创新团队"(2015RA4002)
国家自然科学基金(81403239)
上海市中医药三年行动计划项目(ZY3-CCCX-2-1002)
上海高校实验技术队伍建设计划(lh01.24.001)
