title: Hedgehog signaling and osteoblast gene expression are regulated by purmorphamine in human mesenchymal stem cells.
abstract: Several biological events are controlled by Hedgehog (Hh) signaling, including osteoblast phenotype development. This study aimed at evaluating the gene expression profile of human mesenchymal stem cells (hMSCs) treated with the Hh agonist, purmorphamine, focusing on Hh signaling and osteoblast differentiation. hMSCs from bone marrow were cultured in non-osteogenic medium with or without purmorphamine (2 µM) for periods of up to 14 days. Purmorphamine up-regulated gene expression of the mediators of Hh pathway, SMO, PTCH1, GLI1, and GLI2. The activation of Hh pathway by purmorphamine increased the expression of several genes (e.g., RUNX2 and BMPs) related to osteogenesis. Our results indicated that purmorphamine triggers Hh signaling pathway in hMSCs, inducing an increase in the expression of a set of genes involved in the osteoblast differentiation program. Thus, we conclude that Hh is a crucial pathway in the commitment of undifferentiated cells to the osteoblast lineage.
authors: Cell Culture Laboratory, School of Dentistry of Ribeirao Preto, University of Sao Paulo, 14040-904 Ribeirao Preto, Sao Paulo, Brazil.
authors: F S
authors: FS
authors: Oliveira
authors: L S
authors: LS
authors: Bellesini
authors: H L A
authors: HL
authors: Defino
authors: C F
authors: CF
authors: da Silva Herrero
authors: M M
authors: MM
authors: Beloti
authors: A L
authors: AL
authors: Rosa
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D020869:Gene Expression Profiling; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011687:Purines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C400551:GLI1 protein, human; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009025:Morpholines; D009687:Nuclear Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011687:Purines; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; C470893:purmorphamine