| Bone morphogenetic protein 9 is one of the most potent factors which inducing osteogenic differentiation in mesenchymal stem cells,and it has promising clinical application prospects.Previous studies showed that Wnt11 promoted the BMP9-induced bone differentiation in MSCs,but the molecular mechanism keeps unclear.It has been reported that TGF-?1 is involved in Wnt11-induced chondrocyte differentiation in MSCs,but the relationship between Wnt11 and TGF-?1 in BMP9-induced stem cell bone formation is still unclear.The main purpose of this study is to investigate the relationship between Wnt11 and TGF-?1 in BMP9-induced osteogensis and its possible molecular mechanisms.In this experiment,we used histochemical staining,Western blot,RT-PCR,alizarin red staining,ectopic osteogenesis and ?-CT analysis.Firstly,we confirmed the effect of Wnt11 on BMP9-induced C3H10T1/2 cells osteogenic differentiation and the possible molecular mechanisms.Then,we analyzed the effect of Wnt11 and BMP9 on TGF-?1 in C3H10T1/2 cells.Finally,we investigated the relationship between TGF-?1 and BMP9-induced osteogenic differentiation,so did the possible molecular mechanisms.The results showed that exogenous Wnt11 promoted BMP9-induced osteogenic differentiation and increased p38 MAPK phosphorylation levels in C3H10T1/2 cells;Wnt11 promoted TGF-?1 expression when BMP9 induce osteogenic differentiation in C3H10T1/2 cells;BMP9 increased the expression of TGF-?1,and it enhanced the level of osteogenic markers induced by BMP9;TGF-?1 promoted phosphorylation of Smad2/3,and up-regulated the level of p-p38 MAPK;Inhibitor of p38 MAPK significantly reduced the effect of TGF-?1 on BMP9-induced osteogenic differentiation.The results suggest that TGF-?1 can promote BMP9-induced osteogenic differentiation,and may be partly mediated the effect of Wnt11 on BMP9-induced osteogenic differentiation.The mechanism may be related to increase the activation of p38 MAPK signaling. |
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