经典Wnt信号通路对人牙周膜干细胞成骨分化的影响  

Effect of the canonical Wnt signaling pathway on osteogenic differentiation of human periodontal ligament stem cells

作　　者：刘冬巧 王天齐[2,3] 段小妮 颜艳 张淋坤[2,3] 张春香 LIU Dong-qiao;WANG Tian-qi;DUAN Xiao-ni;YAN Yan;ZHANG Lin-kun;ZHANG Chun-xiang(Department of Orthodontics,Zhengzhou Stomatological Hospital,Zhengzhou 450000,China;Department of Stomatology,School of Medicine,Nankai University,Major/Department of Orthodontics,Tianjin 300071,China;Department of Orthodontics,Tianjin Stomatological Hospital,Tianjin Key Laboratory of Oral Function Reconstruction,Tianjin 300041,China;Department of Stomatology,Tianjin Medical University,Major/Department of Orthodontics,Tianjin 300070 China;Central Laboratory of Tianjin Stomatological Hospital,Tianjin300041,China)

机构地区：[1]郑州市口腔医院正畸科,郑州450000 [2]南开大学医学院口腔医学系口腔正畸学,天津300071 [3]天津市口腔医院正畸科,天津市口腔功能重建重点实验室,天津300041 [4]天津医科大学口腔医学系口腔正畸学,天津300070 [5]天津市口腔医院中心实验室,天津300041

出　　处：《西南医科大学学报》2021年第6期633-639,共7页Journal of Southwest Medical University

基　　金：天津市卫生行业重点攻关项目(15KG119);天津市首批卫生计生行业高层次人才选拔培养工程(津人才[2018]19号)。

摘　　要：目的探讨经典Wnt/β-catenin通路对人PDLSCs成骨分化的信号调节。方法本研究从细胞、基因和蛋白水平研究了经典Wnt信号通路对人PDLSCs成骨分化的调控作用。结果经典Wnt通路激活剂氯化锂(LiCl)刺激人PDLSCs后,β-catenin、Osterix和OPG的蛋白表达量相较于对照组增加(P<0.05),呈剂量依赖性上调,分别增大为原对照组的1.7倍、1.2倍和1.2倍。但RANKL的表达没有改变(P>0.05),导致OPG/RANKL比值变大。同时ALP、Col-I和Runx2的mRNA水平也升高(P<0.05),分别增大为原对照组的1.7倍、1.5倍和2倍。用β-catenin抑制剂豆蔻素阻断经典Wnt通路,可促进细胞内β-catenin的降解,降低Osterix和OPG的蛋白表达,以及ALP、Col-I和Runx2的mRNA的表达。结论经典Wnt信号通路对人PDLSCs的成骨分化有正向调节作用,为牙周组织工程中经典Wnt/β-catenin信号通路对人牙周膜干细胞成骨分化的药理学调控提供了一种可行性策略,同时也为促进正畸治疗过程中的牙齿移动以及随后的牙周组织改建提供了思路。Objective To investigate the canonical Wnt/β-catenin signaling regulation of osteogenic differentiation of human periodontal ligament stem cells(PDLSCs).Methods In this study,the regulatory effect of the canonical Wnt signaling pathway on osteogenic differentiation of human PDLSCs were investigated at the cellular,genetic,and protein levels.Results After human PDLSCs were stimulated with lithium chloride(LiCl),a canonical Wnt activator,the expression ofβ-catenin,Osterix,and osteoprotegerin(OPG)proteins was significantly up-regulated in a dose-dependent manner(P<0.05),increasing to 1.7 times,1.2 times and 1.2 times,respectively,that in the original control group,but the expression of receptor activator of nuclear factor-kappa B ligand(RANKL)did not change(P>0.05),resulting in an increased OPG/RANKL ratio.In addition,the mRNA levels of ALP,Col-I,and Runx2 were significantly increased(P<0.05),increasing to 1.7 times,1.5 times and 2 times,respectively,those in the original control group.Blockage of the canonical Wnt signaling pathway with cardamonin,an inhibitor ofβ-catenin,promoted the degradation of intracellularβ-catenin,thereby down-regulating the protein expression of Osterix and OPG and the mRNA expression of ALP,Col-I,and Runx2.Conclusion The canonical Wnt signaling pathway can positively regulate osteogenic differentiation of human PDLSCs,providing a viable strategy for pharmacological modulation of human PDLSC osteogenic differentiation via the canonical Wnt/β-catenin signaling pathway in periodontal tissue engineering,as well as providing ideas for accelerating tooth movement and subsequent periodontal tissue remodeling during orthodontic treatment.

关 键 词：骨生物学 细胞/分子生物学 保持和稳定性 WNT/Β-CATENIN信号通路 人牙周膜干细胞 

分 类 号：R783.5[医药卫生—口腔医学]