Sprouty2 is involved in the control of osteoblast proliferation and differentiation through the FGF and BMP signaling pathways.
Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified. In this study, we investigated the involvement of Sprouty2 in osteoblast proliferation and differentiation. We examined Sprouty2 expression in MC3T3-E1 cells, and found that high levels of Sprouty2 expression were induced by basic FGF stimulation. Overexpression of Sprouty2 in MC3T3-E1 cells resulted in suppressed proliferation compared with control cells. Sprouty2 negatively regulated the phosphorylation of ERK1/2 after basic FGF stimulation, and of Smad1/5/8 after BMP stimulation. Furthermore, Sprouty2 suppressed the expression of osterix, alkaline phosphatase, and osteocalcin mRNA, which are markers of osteoblast differentiation. Additionally, Sprouty2 inhibited osteoblast matrix mineralization. These results suggest that Sprouty2 is involved in the control of osteoblast proliferation and differentiation by downregulating the FGF-ERK1/2 and BMP-Smad pathways, and suppresses the induction of markers of osteoblast differentiation.
['Taketomi|Takaharu|T|', 'Onimura|Tomohiro|T|', 'Yoshiga|Daigo|D|', 'Muratsu|Daichi|D|', 'Sanui|Terukazu|T|', 'Fukuda|Takao|T|', 'Kusukawa|Jingo|J|', 'Nakamura|Seiji|S|']
D016475:3T3 Cells D000818:Animals D055396:Bone Morphogenetic Protein 2 D019485:Bone Morphogenetic Proteins D002454:Cell Differentiation D002460:Cell Line D049109:Cell Proliferation D016222:Fibroblast Growth Factor 2 D005346:Fibroblast Growth Factors D047908:Intracellular Signaling Peptides and Proteins D020935:MAP Kinase Signaling System D008565:Membrane Proteins D051379:Mice D008810:Mice, Inbred C57BL D008813:Mice, Inbred ICR D010006:Osteoblasts D015675:Osteocalcin D010012:Osteogenesis D017346:Protein Serine-Threonine Kinases D015398:Signal Transduction D051785:Smad Proteins D000076182:Sp7 Transcription Factor
osteoblast fibroblast growth factor bone morphogenetic protein sprouty