title: Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells.
abstract: We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKO(ob)) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKO(ob) mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKO(ob) osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA(+) MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells.
authors.affiliation: Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Wuchen
authors.initials: W
authors.lastname: Yang
authors.forename: Dayong
authors.initials: D
authors.lastname: Guo
authors.forename: Marie A
authors.initials: MA
authors.lastname: Harris
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Jelica
authors.initials: J
authors.lastname: Gluhak-Heinrich
authors.forename: Junjie
authors.initials: J
authors.lastname: Wu
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
authors.forename: Charles
authors.initials: C
authors.lastname: Skinner
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
authors.forename: James R
authors.initials: JR
authors.lastname: Edwards
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Mundy
authors.forename: Alex
authors.initials: A
authors.lastname: Lichtler
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Kream
authors.forename: David W
authors.initials: DW
authors.lastname: Rowe
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
authors.forename: Val
authors.initials: V
authors.lastname: David
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Quarles
authors.forename: Demetri
authors.initials: D
authors.lastname: Villareal
authors.forename: Greg
authors.initials: G
authors.lastname: Scott
authors.forename: Manas
authors.initials: M
authors.lastname: Ray
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Harris
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010521:Periosteum; D015398:Signal Transduction
chemical_list: D055396:Bone Morphogenetic Protein 2
keywords: Angiogenesis; Bmp2; Mesenchymal stem cells; Osteoblasts; VegfA; α-SMA+ cells