TRAF6/Runx2信号轴对牙龈卟啉单胞菌诱导血管平滑肌细胞钙化调控作用的研究  

Porphyromonas Gingivalis Induce Vascular Smooth Muscle Cells Calcification though Regulation of TRAF6/Runx2 Pathway

作　　者：唐路[1] 杨文文 张献丽 张欣然 薛栋[1] 冷丽君 赵颖[1] TANG Lu;YANG Wenwen;ZHANG Xianli;ZHANG Xinran;XUE Dong;LENG Lijun;ZHAO Ying(Department of Dentistry,Xuanwu Hospital,Capital Medical University,Beijing 100053,China.)

机构地区：[1]首都医科大学宣武医院口腔科,北京100053

出　　处：《口腔医学研究》2024年第5期401-406,共6页Journal of Oral Science Research

基　　金：北京市医管局培育基金(编号:PX2023033);北京市医管局“青苗计划”(编号:QML201808087)。

摘　　要：目的:探讨肿瘤坏死因子受体相关因子6(tumor necrosis factor receptor-associated factor 6,TRAF6)/Runt-相关转录因子-2(Runt-related-transcription factor-2,Runx2)信号轴对牙龈卟啉单胞菌(P.gingivalis)诱导小鼠血管平滑肌细胞(vascular smooth muscle cell,VSMC)钙化的调控作用。方法:用热灭活的P.gingivalis和VSMC共培养,在21 d时检测VSMC的钙化沉积和钙含量;并检测VSMC收缩标志物α-平滑肌肌动蛋白(alpha smooth muscle actin,α-SMA)和平滑肌22α(smooth muscle 22 alpha,SM22α),以及成骨标志物碱性磷酸酶(alkaline phosphatase,ALP)、骨钙素(osteocalcin,OC)和Ⅰ型胶原A1(type I collagen A1,ColⅠA1)的基因和蛋白表达。此外,检测P.gingivalis诱导VSMC后TRAF6和Runx2的表达,进一步通过抑制TRAF6,检测其对Runx2表达以及VSMC和主动脉的钙化情况的作用。结果:P.gingivalis可促进VSMC发生钙化沉积以及钙含量增加(P<0.05);并且P.gingivalis能显著促进成骨标志物的表达,抑制VSMC收缩标志物表达(P<0.05);当抑制TRAF6表达时,能降低P.gingivalis诱导VMSC中Runx2的表达,并抑制VSMC和主动脉壁的钙化沉积,显著降低VSMC中钙含量(P<0.05)。结论:P.gingivalis促进VSMC成骨标志物表达,抑制收缩标志物表达,最终诱导VSMC发生钙化;并进一步证实P.gingivalis可通过TRAF6/Runx2信号轴调控VSMC和主动脉钙化。Objective:To explore the regulatory effect of tumor necrosis factor receptor-associated factor 6(TRAF6)/Runt-related-transcription factor-2(Runx2)signaling axis on porphyromonas gingivalis(P.gingivalis)-induced calcification of vascular smooth muscle cells(VSMC).Methods:Heat-inactivated P.gingivalis and VSMC were co-cultured,and the calcification deposition and calcium content of VSMC were detected after 21 days.Gene and protein expression of VSMC contraction markers alpha smooth muscle actin(α-SMA)and smooth muscle 22 alpha(SM22α),as well as osteogenic markers alkaline phosphatase(ALP),osteocalcin(OC),and type I collagen A1(ColⅠA1)were detected.In addition,the expression of TRAF6 and Runx2 after P.gingivalis induced VSMC was detected,and its effect on Runx2 expression and calcification of VSMC and aorta was further tested by inhibiting TRAF6.Results:P.gingivalis could promote calcification deposition and increase calcium content in VSMC(P<0.05);and P.gingivalis could significantly promote the expression of osteogenic markers and inhibit the expression of VSMC contraction markers(P<0.05).Inhibition of TRAF6 could reduce the expression of Runx2,calcification deposition of VSMC and aortic wall,and the calcium content in VSMC(P<0.05).Conclusion:P.gingivalis promotes the expression of osteogenic markers in VSMC,inhibits the expression of contractile markers,and ultimately induces VSMC calcification.P.gingivalis can induce VSMC and aortic calcification through the TRAF6/Runx2 signaling axis.

关 键 词：牙龈卟啉单胞菌 血管平滑肌细胞 血管钙化 牙周炎 动脉粥样硬化 

分 类 号：R781[医药卫生—口腔医学]