Unloading-Induced Cortical Bone Loss is Exacerbated by Low-Dose Irradiation During a Simulated Deep Space Exploration Mission
- 25 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Calcified Tissue International
- Vol. 107 (2), 170-179
- https://doi.org/10.1007/s00223-020-00708-0
Abstract
Spaceflight-induced bone losses have been reliably reproduced in Hind-Limb-Unloading (HLU) rodent models. However, a considerable knowledge gap exists regarding the effects of low-dose radiation and microgravity together. Ten-week-old male C57BL/6J mice, randomly allocated to Control (CONT), Hind-Limb Unloading (HLU), and Hind-Limb Unloading plus Irradiation (HLUIR), were acclimatized at 28 °C, close to thermoneutral temperature, for 28 days prior to the 14-day HLU protocol. HLUIR mice received a 25 mGy dose of X-ray irradiation, simulating 14 days of exposure to the deep space radiation environment, on day 7 of the HLU protocol. Trabecular bone mass was similarly reduced in HLU and HLUIR mice when compared to CONT, with losses driven by osteoclastic bone resorption rather than changes to osteoblastic bone formation. Femoral cortical thickness was reduced only in the HLUIR mice (102 μm, 97.5–107) as compared to CONT (108.5 μm, 102.5–120.5). Bone surface area was also reduced only in the HLUIR group, with no difference between HLU and CONT. Cortical losses were driven by osteoclastic resorption on the posterior endosteal surface of the distal femoral diaphysis, with no increase in the numbers of dead osteocytes. In conclusion, we show that low-dose radiation exposure negatively influences bone physiology beyond that induced by microgravity alone.Keywords
Funding Information
- Centre National d’Etudes Spatiales (4800000899)
This publication has 28 references indexed in Scilit:
- Hip load capacity cut-points for Astronaut Skeletal Health NASA Finite Element Strength Task Group Recommendationsnpj Microgravity, 2019
- One-month spaceflight compromises the bone microstructure, tissue-level mechanical properties, osteocyte survival and lacunae volume in mature mice skeletonsScientific Reports, 2017
- Osteocyte Apoptosis Caused by Hindlimb Unloading is Required to Trigger Osteocyte RANKL Production and Subsequent Resorption of Cortical and Trabecular Bone in Mice FemursJournal of Bone and Mineral Research, 2016
- Inhibition of Osteocyte Apoptosis Prevents the Increase in Osteocytic Receptor Activator of Nuclear Factor κB Ligand (RANKL) but Does Not Stop Bone Resorption or the Loss of Bone Induced by UnloadingOnline Journal of Public Health Informatics, 2015
- Beta-1 Adrenergic Agonist Treatment Mitigates Negative Changes in Cancellous Bone Microarchitecture and Inhibits Osteocyte Apoptosis during DisusePLOS ONE, 2014
- Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loadingJournal of Bone and Mineral Research, 2012
- Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesisJournal of Bone and Mineral Metabolism, 2010
- β-Adrenergic Blockade and Leptin Replacement Effectively Mitigate Disuse Bone LossJournal of Bone and Mineral Research, 2009
- Osteoclastogenesis Inhibitory Factor/Osteoprotegerin Reduced Bone Loss Induced by Mechanical UnloadingCalcified Tissue International, 2004
- Bone “mass” and the “mechanostat”: A proposalThe Anatomical Record, 1987