title: Cell-matrix signals specify bone endothelial cells during developmental osteogenesis.
abstract: Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations. The differentiation and functional properties of bone endothelial cells require cell-matrix signalling interactions. Loss of endothelial integrin β1 leads to endothelial cell differentiation defects and impaired postnatal bone growth, which is, in part, phenocopied by endothelial cell-specific laminin α5 mutants. Our work outlines fundamental principles of vessel formation and endothelial cell differentiation in the developing skeletal system.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Urs H
authors.initials: UH
authors.lastname: Langen
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Mara E
authors.initials: ME
authors.lastname: Pitulescu
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Jung Mo
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Research Group Regulatory Genomics, D-48149 Münster, Germany.
authors.forename: Rocio
authors.initials: R
authors.lastname: Enriquez-Gasca
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Kishor K
authors.initials: KK
authors.lastname: Sivaraj
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Anjali P
authors.initials: AP
authors.lastname: Kusumbe
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.|Max Planck Institute for Molecular Biomedicine, Research Group Regulatory Genomics, D-48149 Münster, Germany.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
authors.forename: Jacopo
authors.identifier: 0000-0001-6731-9612
authors.initials: J
authors.lastname: Di Russo
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: M Gabriele
authors.initials: MG
authors.lastname: Bixel
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Cluster of Excellence, University of Münster, D-48149 Münster, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Research Group Regulatory Genomics, D-48149 Münster, Germany.
authors.forename: Juan M
authors.identifier: 0000-0002-6583-6541
authors.initials: JM
authors.lastname: Vaquerizas
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Ralf H
authors.identifier: 0000-0003-3031-7677
authors.initials: RH
authors.lastname: Adams
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D000073861:Apelin; D001842:Bone and Bones / Q000098:blood supply / Q000166:cytology* / Q000000981:diagnostic imaging; D002196:Capillaries / Q000166:cytology; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D010641:Phenotype; D015398:Signal Transduction; D055114:X-Ray Microtomography
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; C045073:Cre recombinase; D019426:Integrases