Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice

Space is a high-stress environment. One major risk factor for the astronauts when they leave the Earth’s magnetic field is exposure to ionizing radiation from galactic cosmic rays (GCR). Several adverse changes occur in mammalian anatomy and physiology in space, including bone loss. In this study, w...

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Autores principales:	Ha-Neui Kim, Kimberly K. Richardson, Kimberly J. Krager, Wen Ling, Pilar Simmons, Antino R. Allen, Nukhet Aykin-Burns
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	galactic cosmic rays space radiation bone loss osteoclast osteoblast mitochondria Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/ea5509a57bbc4d969257a54e3e8efaf2
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id	oai:doaj.org-article:ea5509a57bbc4d969257a54e3e8efaf2
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spelling	oai:doaj.org-article:ea5509a57bbc4d969257a54e3e8efaf22021-11-11T17:10:08ZSimulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice10.3390/ijms2221117111422-00671661-6596https://doaj.org/article/ea5509a57bbc4d969257a54e3e8efaf22021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11711https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Space is a high-stress environment. One major risk factor for the astronauts when they leave the Earth’s magnetic field is exposure to ionizing radiation from galactic cosmic rays (GCR). Several adverse changes occur in mammalian anatomy and physiology in space, including bone loss. In this study, we assessed the effects of simplified GCR exposure on skeletal health in vivo. Three months following exposure to 0.5 Gy total body simulated GCR, blood, bone marrow and tissue were collected from 9 months old male mice. The key findings from our cell and tissue analysis are (1) GCR induced femoral trabecular bone loss in adult mice but had no effect on spinal trabecular bone. (2) GCR increased circulating osteoclast differentiation markers and osteoclast formation but did not alter new bone formation or osteoblast differentiation. (3) Steady-state levels of mitochondrial reactive oxygen species, mitochondrial and non-mitochondrial respiration were increased without any changes in mitochondrial mass in pre-osteoclasts after GCR exposure. (4) Alterations in substrate utilization following GCR exposure in pre-osteoclasts suggested a metabolic rewiring of mitochondria. Taken together, targeting radiation-mediated mitochondrial metabolic reprogramming of osteoclasts could be speculated as a viable therapeutic strategy for space travel induced bone loss.Ha-Neui KimKimberly K. RichardsonKimberly J. KragerWen LingPilar SimmonsAntino R. AllenNukhet Aykin-BurnsMDPI AGarticlegalactic cosmic raysspace radiationbone lossosteoclastosteoblastmitochondriaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11711, p 11711 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	galactic cosmic rays space radiation bone loss osteoclast osteoblast mitochondria Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	galactic cosmic rays space radiation bone loss osteoclast osteoblast mitochondria Biology (General) QH301-705.5 Chemistry QD1-999 Ha-Neui Kim Kimberly K. Richardson Kimberly J. Krager Wen Ling Pilar Simmons Antino R. Allen Nukhet Aykin-Burns Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice
description	Space is a high-stress environment. One major risk factor for the astronauts when they leave the Earth’s magnetic field is exposure to ionizing radiation from galactic cosmic rays (GCR). Several adverse changes occur in mammalian anatomy and physiology in space, including bone loss. In this study, we assessed the effects of simplified GCR exposure on skeletal health in vivo. Three months following exposure to 0.5 Gy total body simulated GCR, blood, bone marrow and tissue were collected from 9 months old male mice. The key findings from our cell and tissue analysis are (1) GCR induced femoral trabecular bone loss in adult mice but had no effect on spinal trabecular bone. (2) GCR increased circulating osteoclast differentiation markers and osteoclast formation but did not alter new bone formation or osteoblast differentiation. (3) Steady-state levels of mitochondrial reactive oxygen species, mitochondrial and non-mitochondrial respiration were increased without any changes in mitochondrial mass in pre-osteoclasts after GCR exposure. (4) Alterations in substrate utilization following GCR exposure in pre-osteoclasts suggested a metabolic rewiring of mitochondria. Taken together, targeting radiation-mediated mitochondrial metabolic reprogramming of osteoclasts could be speculated as a viable therapeutic strategy for space travel induced bone loss.
format	article
author	Ha-Neui Kim Kimberly K. Richardson Kimberly J. Krager Wen Ling Pilar Simmons Antino R. Allen Nukhet Aykin-Burns
author_facet	Ha-Neui Kim Kimberly K. Richardson Kimberly J. Krager Wen Ling Pilar Simmons Antino R. Allen Nukhet Aykin-Burns
author_sort	Ha-Neui Kim
title	Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice
title_short	Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice
title_full	Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice
title_fullStr	Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice
title_full_unstemmed	Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice
title_sort	simulated galactic cosmic rays modify mitochondrial metabolism in osteoclasts, increase osteoclastogenesis and cause trabecular bone loss in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ea5509a57bbc4d969257a54e3e8efaf2
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Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice

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