Diminished response to in vivo mechanical loading in trabecular and not cortical bone in adulthood of female C57Bl/6 mice coincides with a reduction in deformation to load |
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| Affiliation: | 1. Julius Wolff Institut, Charité-Universitätsmedizin Berlin, Germany;2. Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Germany;3. Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA;4. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA;1. Department of Biology, St. Olaf College, Northfield, MN, USA;2. Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA;1. University of Texas – MD Anderson Cancer Center, Department of Endocrine, Neoplasia and Hormonal Disorders, Houston, TX, USA;2. Indiana University, Department of Physical Therapy, Indianapolis, IN, USA;3. Stony Brook University, Department of Biomedical Engineering, Stony Brook, NY, USA;1. Bone and Joint Center, Henry Ford Hospital, Detroit, MI 48202, USA;2. Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA;3. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA;4. Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA;1. Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany;2. Research Centre, Shriners Hospital for Children-Canada, Montreal, Canada;3. Department of Pediatric Surgery, McGill University, Montreal, Canada;4. Julius Wolff Institute & Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health and Charité-Universitätsmedizin Berlin, Berlin, Germany;5. Biodonostia Health Research Institute, Group of Bioengineering in Regeneration and Cancer, San Sebastian, Spain;6. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain |
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| Abstract: | Bone loss occurs during adulthood in both women and men and affects trabecular bone more than cortical bone. The mechanism responsible for trabecular bone loss during adulthood remains unexplained, but may be due at least in part to a reduced mechanoresponsiveness. We hypothesized that trabecular and cortical bone would respond anabolically to loading and that the bone response to mechanical loading would be reduced and the onset delayed in adult compared to postpubescent mice. We evaluated the longitudinal adaptive response of trabecular and cortical bone in postpubescent, young (10 week old) and adult (26 week old) female C57Bl/6J mice to axial tibial compression using in vivo microCT (days 0, 5, 10, and 15) and dynamic histomorphometry (day 15). Loading elicited an anabolic response in both trabecular and cortical bone in young and adult mice. As hypothesized, trabecular bone in adult mice exhibited a reduced and delayed response to loading compared to the young mice, apparent in trabecular bone volume fraction and architecture after 10 days. No difference in mechanoresponsiveness of the cortical bone was observed between young and adult mice. Finite element analysis showed that load-induced strain was reduced with age. Our results suggest that trabecular bone loss that occurs in adulthood may in part be due to a reduced mechanoresponsiveness in this tissue and/or a reduction in the induced tissue deformation which occurs during habitual loading. Therapeutic approaches that address the mechanoresponsiveness of the bone tissue may be a promising and alternate strategy to maintain trabecular bone mass during aging. |
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