Heterotopic bone formation derived from multipotent stromal cells is not inhibited in aged mice |
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| Institution: | 1. Centre de Recherche du CHU Ste-Justine, Université de Montréal, Montréal, Québec, Canada;2. Département de Pharmacologie, Université de Montréal, Montréal, Québec, Canada;3. Département de Somatologie, Université de Montréal, Montréal, Québec, Canada;1. Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, “C. Mondino” National Neurological Institute, Pavia, Italy;2. Department of Brain and Behavior, University of Pavia, Italy;3. Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, “C. Mondino” National Neurological Institute, Pavia, Italy;4. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy;1. Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt;2. Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt;3. Department of Radiodiagnosis, Faculty of Medicine, Ain Shams University, Cairo, Egypt;1. Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany;2. Helmholtz Centre for Infection Research, Braunschweig, Germany;3. Leibniz Institute for Age Research – Fritz Lipmann Institute, Jena, Germany;4. Institute of Transfusion Medicine, University Hospital Jena, Jena, Germany;5. Johannes Gutenberg University, Mainz, Germany;6. Kekulé-Institut für Organische Chemie und Biochemie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Bonn, Germany;7. Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Pharmazeutical Biotechnology, Saarland University, Saarbrücken, Germany;1. Department of Pharmacology and Experimental Therapeutics, Medical Research Institute, Alexandria University, Alexandria, Egypt;2. Department of Pharmaceutics, Alexandria University, Alexandria, Egypt;3. Department of Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt;1. Department of General, Thoracic, Vascular and Transplantation Surgery, University of Rostock, Schillingallee 35, D-18057 Rostock, Germany;2. Institute for Biomedical Engineering, University of Rostock, Friedrich-Barnewitz-Str. 4, D-18119 Rostock, Germany;3. Institute of Pathology, University of Rostock, Strempelstr. 14, D-18055 Rostock, Germany;4. Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, D-18057 Rostock, Germany;1. Department of Pharmacology, JSS College of Pharmacy, Udhagamandalam, The Nilgiris 643001, Tamilnadu, India;2. Molecular Pharmacology and Therapeutics, Mayo Clinic, Rochester, MN, USA;3. Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Udhagamandalam, India;4. Department of Biochemistry, JSS Medical College, JSS University, Mysore, India |
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| Abstract: | Background aimsDecreased bone formation with age is believed to arise, at least in part, because of the influence of the senescent microenvironment. In this context, it is unclear whether multipotent stromal cell (MSC)-based therapies would be effective for the treatment of bone diseases.MethodsWith the use of a heterotopic bone formation model, we investigated whether MSC-derived osteogenesis is impaired in aged mice compared with young mice.ResultsWe found that bone formation derived from MSCs is not reduced in aged mice. These results are supported by the unexpected finding that conditioned media collected from ionizing radiation–induced senescent MSCs can stimulate mineralization and delay osteoclastogenesis in vitro.ConclusionsOverall, our results suggest that impaired bone formation with age is mainly cell-autonomous and provide a rationale for the use of MSC-based therapies for the treatment of bone diseases in the elderly. |
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| Keywords: | aging heterotopic bone ionizing radiation MSC senescence |
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