title: Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
abstract: The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice. At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+. Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants. At d6, a much higher number of Lin-(×3) as well as LSK (Lin-IL-7Rα-Sca-1hic-Kithi, ×2) and hematopoietic stem cells (HSC: Flt3-LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization. However, the proportion of LSK and HSC within the Lin-was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP. Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants. In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation. Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN. J. Cell. Physiol. 232: 2528-2537, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Wafa
authors.initials: W
authors.lastname: Bouleftour
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Renata Neves
authors.initials: RN
authors.lastname: Granito
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanden-Bossche
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.|Flow Cytometry Facility, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Sabido
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Roche
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Linossier
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.affiliation: Laboratoire de Biologie des Tissus Ostéoarticulaires, INSERM, U1059 Sainbiose, Université de Lyon, Université Jean Monnet, Faculté de Médecine, Campus Santé Innovation, Saint-Étienne, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005838:Genotype; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058574:Integrin-Binding Sialoprotein / Q000172:deficiency* / Q000235:genetics; D008297:Male; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; C506896:Spp1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053495:Osteopontin