Study On The Relationship Between COX-2 And Bmp9-induced Osteogenic/adipogenic Differentiation In Mesenchymal Stem Cells

Osteogenic differentiation and adipogenic differentiation maintain a dynamic balance during bone development.The imbalance between osteogenic and adipogenic diffierentiation will cause a series of bone-related diseases.BMP9,as an efficacious osteogenic factor,it can also induces adipogenic differentiation in MSCs.Therefore,inhibition of BMP9-induced adipogenesis in MSCs may enhance the BMP9-induced osteogenesis.Our previous studies have shown that NS-398,a COX-2inhibitor,can inhibit BMP9-induced osteogenic differentiation of MSCs and promote adipogenic differentiation.But the concrete molecular mechanism underlying this biological process keeps unclear still.This study explored the possible relationship between COX-2 and BMP9-induced adipogenesis in MSCs and the possible molecular mechanisms about this process.Western blot,oil red O staining and ectopic osteogenesis experiment and other experimental methods were used for this research.Results showed that COX-2 inhibitor(NS-398)can inhibit BMP9-induced osteogenic differentiation and promote BMP9-inducedadipogenic differentiation;Exogenous β-catenin can enhance the potential of BMP9 to induce osteogenic differentiation but reduce the ability to induce adipogenesis;BMP9 increases the mRNA expression of c-myc andβ-catenin in C3H10T1/2 cells,which was attenuated by NS-398;Exogenous β-catenin reverses the effect of NS-398 on BMP9-induced osteogenic and adipogenic differentiation in C3H10T1/2 cells.In addition,BMP9 up-regulates the mRNA expression level of LRP6.LRP6 promotes BMP9’s potential to induce osteogenic differentiation in C3H10T1/2 cells,but showing reversal effect on adipogenic differentiation in C3H10T1/2cells.The effect of BMP9 on LRP6 was significantly reduced by NS-398.These datas indicated that COX-2 may promote BMP9’s osteogenic potential at the expense of adipogenic differentiation.The process may be mediated through up-regulating LRP6 to enhance the activation of Wnt/β-catenin pathway.