Platelet-derived growth factor receptor kinase inhibitor AG-1295 promotes osteoblast differentiation in MC3T3-E1 cells via the Erk pathway.
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.
Shandong Academy of Medical Sciences, Shandong Medical Biotechnological Center, Key Laboratory for Rare Disease Research of Shandong Province, Ji'nan, Shandong, China.
Y Y
YY
Zhang
Y Z
YZ
Cui
J
J
Luan
X Y
XY
Zhou
G L
GL
Zhang
J X
JX
Han
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*
C407689:6,7-dimethoxy-2-phenylquinoxaline; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D005994:Glycerophosphates; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D020032:Tyrphostins; D015675:Osteocalcin; D003907:Dexamethasone; D020797:Receptor, Platelet-Derived Growth Factor beta; C510878:ALPL protein, mouse; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid