Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone.

Autor: Lang A; Departments of Orthopaedic Surgery and Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA. annemarie.lang@tu-dresden.de.; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany. annemarie.lang@tu-dresden.de.; Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden (TUD), Fetscherstrasse 74, Dresden, 01307, Germany. annemarie.lang@tu-dresden.de., Benn A; Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, Leuven, 3000, Belgium.; VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Leuven, 3000, Belgium., Collins JM; Departments of Orthopaedic Surgery and Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA., Wolter A; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany.; Department of Veterinary Medicine, Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin, Berlin, 14163, Germany., Balcaen T; Institute of Mechanics, Materials and Civil Engineering, Biomechanics lab, UCLouvain, Louvain-la-Neuve, 1348, Belgium.; Institute of Experimental and Clinical Research, Pole of Morphology, UCLouvain, Brussels, 1200, Belgium.; KU Leuven, Department of Chemistry, Sustainable Chemistry for Metals and Molecules, Leuven, 3000, Belgium., Kerckhofs G; Institute of Mechanics, Materials and Civil Engineering, Biomechanics lab, UCLouvain, Louvain-la-Neuve, 1348, Belgium.; Institute of Experimental and Clinical Research, Pole of Morphology, UCLouvain, Brussels, 1200, Belgium.; Department of Materials Engineering, KU Leuven, Heverlee, 3001, Belgium.; Division for Skeletal Tissue Engineering, Prometheus, KU Leuven, Leuven, 3000, Belgium., Zwijsen A; Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, Leuven, 3000, Belgium., Boerckel JD; Departments of Orthopaedic Surgery and Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA. boerckel@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Mar 13; Vol. 7 (1), pp. 315. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.1038/s42003-024-05915-1
Abstrakt: Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone formation in part by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered trabecular and cortical bone formation. SMAD1/5 depletion induced excessive sprouting and disrupting the morphology of the metaphyseal vessels, with impaired anastomotic loop formation at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long-term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops and elevated vascular permeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics in juvenile mouse bone.
(© 2024. The Author(s).)
Databáze: MEDLINE
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