Initiation of Early Osteoblast Differentiation Events through the Direct Transcriptional Regulation of Msx2 by FOXC1

摘要: Hierarchal transcriptional regulatory networks function to control the correct spatiotemporal patterning of mammalian skeletal system. One such factor, forkhead box transcription factor FOXC1 is necessary for formation axial and craniofacial skeleton. Previous studies have demonstrated that frontal parietal bones skull fail develop in mice deficient Foxc1. Furthermore expression Msx2 homeobox gene, an essential regulator calvarial bone development absent mesenchymal progenitors Foxc1 mutant mice. Thus we sought determine whether was a direct target regulation. Here, demonstrate elevated can increase endogenous mRNA levels. Chromatin immunoprecipitation experiments reveal occupies conserved element MSX2 promoter. Using luciferase reporter assay, stimulate activity both human mouse promoters. We also report reducing levels by RNA interference leads decrease expression. Finally, heterologous C2C12 cells results alkaline phosphatase increased Runx2 Msx2. These data indicate similar enhanced osteogenic differentiation phenotype as observed with overexpression. Together these findings suggest Foxc1->Msx2 network functions initial stages osteoblast differentiation.