title: Modification of Smad1 linker modulates BMP-mediated osteogenesis of adult human MSC.
abstract: We examined whether bone morphogenetic protein (BMP)-mediated osteogenesis of adult human mesenchymal stem cells (MSCs) is regulated by extracellular signal-regulated kinase phosphorylation of Smad1. Adenoviral constructs carrying either unmodified human Smad1 or Smad1 mutated in the linker region to preclude extracellular signal-regulated kinase phosphorylation were expressed in human and rodent cells. Unlike unmodified Smad1, expression of mutated Smad1 facilitated BMP-stimulated expression of osteoblast markers in human MSC but had no effect on either rat MSC or mouse pre-osteoblastic MC3T3-E1 cells. Expression of mutated Smad1 in adult human MSC cultures also resulted in increased nuclear accumulation of BMP-activated Smads and elevated gene transcripts characteristic of differentiating osteoblasts. These results may partly explain the poor efficacy of BMP in some human bone therapies and indicate an important mechanism regulating BMP-mediated bone formation in adults.
authors.affiliation: Department of Cytology and Histology, Jagiellonian University , Kraków , Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Skarżyńska
authors.forename: Milena
authors.initials: M
authors.lastname: Damulewicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Filipowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Madej
authors.forename: Phoebe S
authors.initials: PS
authors.lastname: Leboy
authors.forename: Anna M
authors.initials: AM
authors.lastname: Osyczka
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008875:Middle Aged; D010012:Osteogenesis / Q000235:genetics*; D010766:Phosphorylation; D051381:Rats; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D051898:Smad1 Protein; D048049:Extracellular Signal-Regulated MAP Kinases