title: Acute exposure to high dose γ-radiation results in transient activation of bone lining cells.
abstract: The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced cancellous bone volume fraction, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14days following γ-irradiation with 6Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14days following irradiation. Marrow cell density decreased within 1day (67% reduction, p<0.0001), reached a minimum value after 3days (86% reduction, p<0.0001), and partially rebounded by 14days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1day, p=0.04), 1230% (3days, p<0.0001), and 530% (14days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation -0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover.
authors: Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR, USA. Electronic address: Russell.Turner@oregonstate.edu.
authors: Russell T
authors: RT
authors: Turner
authors: Urszula T
authors: UT
authors: Iwaniec
authors: Carmen P
authors: CP
authors: Wong
authors: Laurence B
authors: LB
authors: Lindenmaier
authors: Lindsay A
authors: LA
authors: Wagner
authors: Adam J
authors: AJ
authors: Branscum
authors: Scott A
authors: SA
authors: Menn
authors: James
authors: J
authors: Taylor
authors: Ye
authors: Y
authors: Zhang
authors: Honglu
authors: H
authors: Wu
authors: Jean D
authors: JD
authors: Sibonga
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D005260:Female; D005720:Gamma Rays; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000528:radiation effects
keywords: Bone histomorphometry; Bone marrow; Murine; Osteoblasts; Osteoclasts; Osteoporosis
references: Radiat Res. 1994 Apr;138(1 Suppl):S5-8
references: 8146326
references: Bone. 2011 Mar 1;48(3):425-32
references: 21035575
references: South Med J. 2010 Jun;103(6):541-6
references: 20710137
references: Blood. 2009 Sep 10;114(11):2333-43
references: 19433859
references: Bone. 2010 Sep;47(3):472-9
references: 20601290
references: PLoS One. 2012;7(8):e42668
references: 22880075
references: Mol Cell Biochem. 2012 May;364(1-2):271-81
references: 22258824
references: Osteoporos Int. 2004 Sep;15(9):716-23
references: 15052380
references: Radiat Res. 2011 Jul;176(1):e0001-15
references: 21545291
references: Blood. 2003 Apr 1;101(7):2609-16
references: 12468435
references: Endocr Rev. 2008 Jun;29(4):403-40
references: 18451259
references: J Neurosurg Spine. 2012 Apr;16(4):379-86
references: 22225488
references: Nat Rev Rheumatol. 2011 Apr;7(4):235-43
references: 21386794
references: J Biol Chem. 2004 Oct 15;279(42):43667-74
references: 15304475
references: Fertil Steril. 2012 Jan;97(1):134-40.e1
references: 22137491
references: Endocrinology. 2008 Nov;149(11):5735-46
references: 18635661
references: J Radiat Res. 2011;52(6):727-34
references: 21921435
references: Endocr Rev. 1994 Jun;15(3):275-300
references: 8076582
references: J Radiat Res. 2007 Nov;48(6):455-60
references: 17785936
references: Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1 Suppl 2):29-37
references: 21669135
references: Folia Histochem Cytobiol. 2005;43(4):223-7
references: 16382889
references: Bone. 2010 Jan;46(1):101-11
references: 19747571
references: Bone. 1998 Aug;23(2):127-33
references: 9701471
references: Int J Radiat Biol. 2005 Mar;81(3):233-41
references: 16019932
references: Endocrinology. 1995 Aug;136(8):3632-8
references: 7628403
references: Health Phys. 2003 Aug;85(2):150-8
references: 12938961
references: Radiat Res. 2008 Sep;170(3):388-92
references: 18763868
references: Climacteric. 1998 Mar;1(1):72-9
references: 11907930
references: Health Phys. 2011 Nov;101(5):562-5
references: 21979541
references: Endocrinology. 1994 Jan;134(1):461-6
references: 7506213
references: Eur Radiol. 2006 Mar;16(3):619-33
references: 16237551
references: J Bone Miner Res. 1993 Mar;8(3):379-88
references: 8456591
references: Radiat Prot Dosimetry. 2005;115(1-4):44-50
references: 16381680
references: BMC Med. 2011 Nov 25;9:126
references: 22114866
references: Curr Osteoporos Rep. 2011 Jun;9(2):96-102
references: 21360286
references: PLoS One. 2011 Jan 05;6(1):e14486
references: 21245929
references: PLoS One. 2011;6(9):e24072
references: 21935373
references: J Pediatr Hematol Oncol. 2013 May;35(4):e144-8
references: 23211689
references: Acta Obstet Gynecol Scand. 2004 Jan;83(1):96-102
references: 14678092
references: J Natl Cancer Inst Monogr. 2005;(34):64-8
references: 15784827
references: J Am Geriatr Soc. 2010 Dec;58(12):2337-44
references: 21143442
references: Pediatr Transplant. 1999 Feb;3(1):38-44
references: 10359030
references: Int J Gen Med. 2012;5:105-15
references: 22319248
references: Radiographics. 1998 Sep-Oct;18(5):1125-36; quiz 1242-3
references: 9747611
references: Endocrinology. 2005 Sep;146(9):4074-81
references: 15947001
references: Radiat Res. 2008 Jun;169(6):607-14
references: 18494551
references: Stem Cells. 2011 Sep;29(9):1315-21
references: 21755574
references: J Bone Miner Res. 2012 Apr;27(4):749-59
references: 22190044
references: Methods Mol Biol. 2008;447:325-41
references: 18369927
references: Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):37-45
references: 8118384
references: J Long Term Eff Med Implants. 2009;19(4):287-304
references: 21083535
references: J Bone Miner Res. 2010 Apr;25(4):757-68
references: 19821771