title: Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.
abstract: To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling.
authors.affiliation: Centre for Children's Bone Health, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: Mille
authors.initials: M
authors.lastname: Kolind
authors.affiliation: Centre for Children's Bone Health, The Children's Hospital at Westmead, Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Bobyn
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, UConn Health, Farmington, CT, USA.
authors.forename: Brya G
authors.initials: BG
authors.lastname: Matthews
authors.affiliation: Centre for Children's Bone Health, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Mikulec
authors.affiliation: Centre for Children's Bone Health, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: Alastair
authors.initials: A
authors.lastname: Aiken
authors.affiliation: Centre for Children's Bone Health, The Children's Hospital at Westmead, Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Little
authors.affiliation: Department of Reconstructive Sciences, School of Dental Medicine, UConn Health, Farmington, CT, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
authors.affiliation: Centre for Children's Bone Health, The Children's Hospital at Westmead, Westmead, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia. Electronic address: aaron.schindeler@sydney.edu.au.
authors.forename: Aaron
authors.initials: A
authors.lastname: Schindeler
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D019070:Cell Lineage / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D042787:Receptor, TIE-2; C079086:Tek protein, mouse
keywords: BMPs; Bone morphogenetic proteins; Endothelial cells; Lineage tracking; Spine fusion; Tie2; Transgenic reporter mice