title: Skeletal trauma generates systemic BMP2 activation that is temporally related to the mobilization of CD73+ cells.
abstract: The relationship between BMP2 expression and the recruitment of skeletogenic stem cells was assessed following bone marrow reaming. BMP2 expression was examined using transgenic mice in which β-galactosidase had been inserted into the coding region of BMP2. Stem cell mobilization was analyzed by FACS analysis using CD73, a marker associated with bone marrow stromal stem cells. BMP2 expression was induced in endosteal lining cells, cortical osteocytes and periosteal cells in both the reamed and in contralateral bones. BMP2 mRNA expression in the reamed bone showed an early peak within the first 24 h of reaming followed by a later peak at 7 days, while contralateral bones only showed the 7 days peak of expression. FACS analysis sorting on CD73 positive cells showed a 50% increase of these cells at 3 and 14 days in the marrow of the injured bone and a single peak at 14 days of the marrow cell population of the contralateral bone. A ∼20% increase of CD73 positive cells was seen in the peripheral blood 2 days after reaming. These data showed that traumatic bone injury caused a systemic induction of BMP2 expression and that this increase is correlated with the mobilization of CD73 positive cells.
authors.affiliation: Department of Orthopaedic Surgery, Boston University Medical Center, 715 Albany Street, R-205, Boston, 02118, Massachusetts.
authors.forename: Richard
authors.initials: R
authors.lastname: Marsell
authors.forename: Brandon
authors.initials: B
authors.lastname: Steen
authors.forename: Manish V
authors.initials: MV
authors.lastname: Bais
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Mortlock
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Einhorn
authors.forename: Louis C
authors.initials: LC
authors.lastname: Gerstenfeld
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D019650:Hematopoietic Stem Cell Mobilization; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D013977:Tibia / Q000166:cytology / Q000293:injuries* / Q000502:physiology*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D015720:5'-Nucleotidase
keywords: BMP2; CD73; CXCR4; marrow stromal cells; reaming
references.citation: Cells Tissues Organs. 2001;169(3):285-94
references.pmid: 11455125
references.citation: J Orthop Res. 2008 Nov;26(11):1440-8
references.pmid: 18404732
references.citation: J Exp Med. 2009 Oct 26;206(11):2483-96
references.pmid: 19841085
references.citation: Bone. 2012 Jul;51(1):168-80
references.pmid: 22391215
references.citation: J Cell Biochem. 2006 Oct 15;99(3):690-705
references.pmid: 16888804
references.citation: Bone. 2013 Mar;53(1):239-47
references.pmid: 23219944
references.citation: Biochem Biophys Res Commun. 2012 Jan 6;417(1):211-6
references.pmid: 22142851
references.citation: J Orthop Res. 2010 Dec;28(12):1634-42
references.pmid: 20540091
references.citation: J Bone Joint Surg Br. 2007 Jan;89(1):116-20
references.pmid: 17259429
references.citation: Differentiation. 2013 Jan;85(1-2):1-10
references.pmid: 23314286
references.citation: Bone. 2009 Aug;45(2):254-66
references.pmid: 19398045
references.citation: Bone. 2007 May;40(5):1389-98
references.pmid: 17303481
references.citation: Stem Cells. 2009 Aug;27(8):1887-98
references.pmid: 19544445
references.citation: J Biol Chem. 2009 Jun 26;284(26):17564-74
references.pmid: 19406748
references.citation: J Bone Miner Res. 2008 Aug;23(8):1204-16
references.pmid: 18348700
references.citation: N Engl J Med. 2005 May 12;352(19):1959-66
references.pmid: 15888696
references.citation: Matrix Biol. 2006 Jul;25(5):271-81
references.pmid: 16584876
references.citation: Nat Genet. 2006 Dec;38(12):1424-9
references.pmid: 17099713
references.citation: Clin Orthop Relat Res. 1997 Jul;(340):267-75
references.pmid: 9224265
references.citation: Stem Cells. 2008 Jan;26(1):223-34
references.pmid: 17932420
references.citation: J Cell Biochem. 2011 Feb;112(2):666-74
references.pmid: 21268088
references.citation: Mol Cell Biol. 2007 Apr;27(8):2934-51
references.pmid: 17283059