铁过载对Wnt信号诱导的ST2细胞成骨分化的作用及机制  

The Effect and Mechanism of Iron Overload in Wnt Signaling-Induced Osteoblast Differentiation of ST2 Cells

作　　者：罗岑 武异洵 刘忻钰 涂小林[1] LUO Cen;WU Yixun;LIU Xinyu;TU Xiaolin(Institute of Life Science,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学生命科学研究院,重庆400016

出　　处：《中国细胞生物学学报》2021年第5期932-938,共7页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81672118)资助的课题。

摘　　要：该研究探究铁过载对Wnt信号诱导的小鼠骨髓基质细胞(ST2)成骨分化的作用及其可能的机制。采用柠檬酸铁铵(FAC)模拟铁过载微环境,用碱性磷酸酶(ALP)染色及生化定量检测成骨分化水平,qRT-PCR检测成骨分化标志基因Alp、Runx2、Osx、Col1以及Wnt信号靶基因Smad6、CyclinD1、Lef1、BMP4的mRNA表达水平,免疫荧光法检测β-catenin入核情况。结果显示,铁过载剂量依赖性抑制Wnt信号诱导的ST2成骨分化,同时显著降低Wnt信号诱导的成骨分化标志基因及Wnt信号靶基因的表达(P<0.05),且铁过载抑制Wnt信号诱导的β-catenin入核。综上所述,铁过载抑制Wnt信号诱导的ST2细胞成骨基因和Wnt靶基因的表达,并通过抑制β-catenin入核而抑制ST2细胞成骨分化。The aim of this study was to investigate the effect of iron overload on osteoblast differentiation of mouse bone marrow stromal cells(ST2)mediated by Wnt signaling and its possible mechanism.FAC(ferric ammonium citrate)was used to mimic the iron overload microenvironment.The expression and activity of alkaline phosphatase were detected to evaluate osteoblast differentiation level.The mRNA expression of osteoblast marker genes Alp,Runx2,Osx,Col1 and Wnt target genes Smad6,CyclinD1,Lef1,BMP4 were detected by qRT-PCR.Nuclear localization ofβ-catenin in the cells was detected by immunofluorescence.These results showed that iron overload dose-dependently inhibited Wnt signaling-induced osteoblast differentiation of ST2,and significantly reduced the expression of Wnt signaling-induced osteoblast marker genes and Wnt target genes(P<0.05).Besides,iron overload inhibited Wnt signaling-inducedβ-catenin entry into the nucleus.In conclusion,iron overload inhibits the osteoblast differentiation of ST2 induced by Wnt signaling via inhibiting the entry ofβ-catenin into the nucleus.

关 键 词：铁过载 WNT信号 成骨分化 

分 类 号：R580[医药卫生—内分泌]