Relationship between wntll and bmp9-induced osteogenic differentiation in mesenchymal stem cells / 中国药理学通报

ABSTRACT

Aim To investigate the relationship between Wnt11 and the BMP9-induced osteogenic differentiation, and the possible molecular mechanism underlying this process as well. Methods qPCR, histochemical staining and Western blot were used to detect the changes of osteogenic differentiation markers and activities of BMP/Smad and p38 MAPK signal. Luciferase reporter assay was used to detect the activity of BMP/Smad signal. Results BMP9 increased the alkaline phosphatase(ALP) activity, mineralization, expression of osteopontin (OPN) and Wnt11 in C3H10T1/2 cells. Wnt11 was detectable in C3H10T1/2, MEFs, MC3T3-E1 and C2C12 cells. In C3H10T1/2, Wnt11 promoted the effect of BMP9 to increase ALP activity, mineralization, and the expression of Runx-2 and OPN. Wnt11 enhanced the effect of BMP9 on increasing BMP/Smad reporter plasmid transcriptional activity and phosphorylation of Smadl/5/8. Wnt11 also increased the BMP9-induced phosphorylation of p38 MAPK. Inhibition of p38 MAPK attenuated the BMP9-induced ALP activity, mineralization and expression of OPN, but these effects were partially reversed by Wnt11. Conclusions BMP9 can up-regulate Wnt11 in MSCs. Wnt11 can promote the BMP9-induced osteogenic differentiation, which may be mediated by increasing the activity of BMP/Smad and p38 MAPK signaling..