Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse

• Published in: Journal of applied physiology (1985) 2010-01, Vol.108 (1), p.152-161
• Main Authors: Kondo, Hisataka, Yumoto, Kenji, Alwood, Joshua S, Mojarrab, Rose, Wang, Angela, Almeida, Eduardo A. C, Searby, Nancy D, Limoli, Charles L, Globus, Ruth K
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Astronauts; Biological and medical sciences; Bone Resorption - etiology; Bone Resorption - pathology; Bone Resorption - physiopathology; Fundamental and applied biological sciences. Psychology; Gamma Rays; Hindlimb Suspension - adverse effects; Male; Mice; Mice, Inbred C57BL; Musculoskeletal diseases; Osteoclasts - radiation effects; Oxidative Stress - radiation effects; Radiation; Radiation Dosage; Rodents; Stress; Whole-Body Irradiation - adverse effects
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00294.2009

1 Space Biosciences Division, NASA Ames Research Center, Moffett Field; and ; 2 Department of Radiation Oncology, University of California, Irvine, California Submitted 18 March 2009 ; accepted in final form 23 October 2009 Exposure of astronauts in space to radiation during weightlessness may contribute to subsequent bone loss. Gamma irradiation of postpubertal mice rapidly increases the number of bone-resorbing osteoclasts and causes bone loss in cancellous tissue; similar changes occur in skeletal diseases associated with oxidative stress. Therefore, we hypothesized that increased oxidative stress mediates radiation-induced bone loss and that musculoskeletal disuse changes the sensitivity of cancellous tissue to radiation exposure. Musculoskeletal disuse by hindlimb unloading (1 or 2 wk) or total body gamma irradiation (1 or 2 Gy of 137 Cs) of 4-mo-old, male C57BL/6 mice each decreased cancellous bone volume fraction in the proximal tibiae and lumbar vertebrae. The extent of radiation-induced acute cancellous bone loss in tibiae and lumbar vertebrae was similar in normally loaded and hindlimb-unloaded mice. Similarly, osteoclast surface in the tibiae increased 46% as a result of irradiation, 47% as a result of hindlimb unloading, and 64% as a result of irradiation + hindlimb unloading compared with normally loaded mice. Irradiation, but not hindlimb unloading, reduced viability and increased apoptosis of marrow cells and caused oxidative damage to lipids within mineralized tissue. Irradiation also stimulated generation of reactive oxygen species in marrow cells. Furthermore, injection of -lipoic acid, an antioxidant, mitigated the acute bone loss caused by irradiation. Together, these results showed that disuse and gamma irradiation, alone or in combination, caused a similar degree of acute cancellous bone loss and shared a common cellular mechanism of increased bone resorption. Furthermore, irradiation, but not disuse, may increase the number of osteoclasts and the extent of acute bone loss via increased reactive oxygen species production and ensuing oxidative damage, implying different molecular mechanisms. The finding that -lipoic acid protected cancellous tissue from the detrimental effects of irradiation has potential relevance to astronauts and radiotherapy patients. spaceflight; osteopenia; hindlimb unloading; -lipoic acid Address for reprint requests and other correspondence: R. K. Globus, MS 236-7 NASA Ames Research Center, Moffett Field, CA 94