Platelet-derived growth factor receptor kinase inhibitor AG-1295 promotes osteoblast differentiation in MC3T3-E1 cells via the Erk pathway

Abstract

Previous studies have conflicting views on the effect of platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) signaling on osteogenesis. The current study investigated the effect of PDGF receptor-beta (PDGFR-β) inhibition by AG-1295 on the osteogenic differentiation of the mouse pre-osteoblastic cell line MC3T3-E1. Osteogenic differentiation was induced by treatment with β-glycerophosphate, ascorbic acid, and dexamethasone along with or absent AG-1295. Results showed that AG-1295 significantly increased alkaline phosphatase (ALP) activity and enhanced the formation of mineralized nodules in a dose-dependent manner. Furthermore, treatment with AG-1295 resulted in up-regulated mRNA expression of the osteogenic marker genes collagen type I (Col1A), runt-related transcription factor 2 (Runx2), osterix (Osx), tissue-nonspecific alkaline phosphatase (Tnap), and osteocalcin (Ocn). Consistent with its effect on osteoblast differentiation, AG-1295 also significantly suppressed the phosphorylation of Erk1/2 in MC3T3-E1 cells. In conclusion, findings suggest that blocking the PDGFR-β pathway with AG1295 markedly promotes osteoblast differentiation and matrix mineralization in mouse osteoblastic MC3T3-E1 cells and that the Erk1/2 pathway might participate in this process.