Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development |
| |
| Affiliation: | 1. Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia;2. South Australian Health and Medical Research Institute, Adelaide, SA, Australia;3. Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia;4. Division of Haematology, SA Pathology, Adelaide, SA, Australia;5. School of Mechanical Engineering, University of Adelaide, Adelaide, Australia;6. St Vincent''s Institute of Medical Research and Department of Medicine, St Vincent''s Hospital, University of Melbourne, Fitzroy, Vic, Australia;1. RWTH Aachen University Clinics, Aachen, Germany;2. University Clinics Eppendorf, Hamburg, Germany;3. McGill University, Montreal, Canada;1. Service de gynécologie obstétrique et médecine de la reproduction, Hôpital Tenon, AP-HP, Sorbonne Université, 4 rue de la Chine, Paris 75020, France;2. INSERM UMRS 938, Faculté de médecine Pierre et Marie Curie, Site Saint-Antoine, 27 rue Chaligny, PARIS cedex 12 75571, France;3. Service d''anatomopathologie, Hôpital Tenon, AP-HP, Sorbonne Université, 4 rue de la Chine, Paris 75020, France;4. Service de chirurgie et cancérologie gynécologique et mammaire, Hôpitaux Universitaires Pitié-Salpêtrière, Charles-Foix, Sorbonne Université, 47/83, boulevard de l''Hôpital, Paris 75013, France;5. Cerba Laboratory, Cergy Pontoise 95066, France;6. Service de médecine interne, Hôpital Saint Antoine, AP-HP, 184 rue du Faubourg Saint Antoine, Sorbonne Université, Paris 75012, France;7. Service de gynécologie obstétrique, CHU de Bicêtre, AP-HP, 78, rue du Général-Leclerc, Le Kremlin-Bicêtre 94270, France;8. Service de gynécologie obstétrique, CHU de Bichat, AP-HP, Paris 75018, France;9. Faculté de médecine Paris 5 Descartes, 12 rue de l''Ecole de Médecine, Paris 75006, France;1. Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, United States;2. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, United States;3. Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands;1. University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States;2. University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States;3. Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Disorders, NIH, Bethesda, MD, United States |
| |
| Abstract: | The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1fl/fl) in osteogenic progenitor cells, under the control of the osterix (Osx:Cre) promoter. The Osx:EfnB1−/− mice displayed aberrant bone growth during embryonic and postnatal skeletal development up to 4 weeks of age, when compared to the Osx:Cre controls. Furthermore, compared to the Osx:Cre control mice, the Osx:EfnB1−/− mice exhibited significantly weaker and less rigid bones, with a reduction in trabecular/ cortical bone formation, reduced trabecular architecture and a reduction in the size of the growth plates at the distal end of the femora from newborn through to 4 weeks of age. The aberrant bone formation correlated with increased numbers of tartrate resistant acid phosphatase positive osteoclasts and decreased numbers of bone lining osteoblasts in 4 week old Osx:EfnB1−/− mice, compared to Osx:Cre control mice. Taken together, these observations demonstrate the importance of ephrinB1 signalling between cells of the skeleton required for endochondral ossification. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
