The Effect and Mechanism of Iron Overload in Wnt Signaling-Induced Osteoblast Differentiation of ST2 Cells
LUO Cen, WU Yixun, LIU Xinyu, TU Xiaolin*
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 of β-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-induced β-catenin entry into the nucleus. In conclusion, iron overload inhibits the osteoblast differentiation of ST2 induced by Wnt signaling via inhibiting the entry of β-catenin into the nucleus.
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