Journal of Radiation Protection and Research

The Korean Association for Radiation Protection (대한방사선방어학회)
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Establishment of a Murine Model for Radiation-induced Bone Loss in Growing C3H/HeN Mice

성장기 마우스에서 방사선 유도 골소실 동물모델 확립

  • Jang, Jong-Sik (College of Ecology and Environmental Science, Kyungpook National University) ;
  • Moon, Changjong (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Jong-Choon (College of Veterinary Medicine, Chonnam National University) ;
  • Bae, Chun-Sik (College of Veterinary Medicine, Chonnam National University) ;
  • Kang, Seong-Soo (College of Veterinary Medicine, Chonnam National University) ;
  • Jung, Uhee (Advanced Radiation Technology Institute) ;
  • Jo, Sung-Kee (Advanced Radiation Technology Institute) ;
  • Kim, Sung-Ho (College of Veterinary Medicine, Chonnam National University)
  • Received : 2014.10.30
  • Accepted : 2015.01.26
  • Published : 2015.03.31
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Abstract

Bone changes are common sequela of irradiation in growing animal. The purpose of this study was to establish an experimental model of radiation-induced bone loss in growing mice using micro-computed tomography (${\mu}CT$). The extent of changes following 2 Gy gamma irradiation ($2Gy{\cdot}min^{-1}$) was studied at 4, 8 or 12 weeks after exposure. Mice that received 0.5, 1.0, 2.0 or 4.0 Gy of gamma-rays were examined 8 weeks after irradiation. Tibiae were analyzed using ${\mu}CT$. Serum alkaline phosphatase (ALP) and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 8 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%) = $0.9584D^2-6.0168D+20.377$ ($r^2$ = 0.946, D = dose in Gy) and BMD ($mg{\cdot}cm^{-3}$) = $8.8115D^2-56.197D+194.41$ ($r^2$ = 0.999, D = dose in Gy). Body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum ALP and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.

성장기 동물에서 방사선 노출은 뼈의 변화를 일으킨다. 본 연구에서는 성장기 동물에서 방사선 유도 골소실 연구를 위한 동물모델을 확립하고자하였다. 성장기(4주령) 마우스에 방사선 노출(2 Gy) 후 시간경과(4, 8 및 12주)에 따른 경골 해면뼈 및 치밀뼈의 변화를 관찰하고, 방사선 비노출군과의 차이가 확연한 방사선 노출 후 8주에 방사선(0.5, 1.0, 2.0 및 4.0 Gy)을 조사하고 조사선량에 따른 변화를 관찰하였다. 동물의 희생 전 악력을 측정하였으며, 경골의 해면뼈 및 치밀뼈를 미세단층촬영 분석하였고, 해면뼈에서 뼈파괴세포의 활성도를 관찰하였다. 혈청내 alkaline phosphatase(ALP) 농도 및 경골의 물리적 강도를 측정하였다. 해면뼈의 확연한 차이는 8주에 관찰되었으며, 조사선량증가에 비례하여 해면뼈량(trabecular bone volume, BV/TV) 및 골밀도(bone mineral density, BMD)의 감소가 관찰되었다. 방사선조사선량에 따른 변화를 나타내는 이차방정식은 BV/TV (%) = $0.9584D^2-6.0168D+20.377$ ($r^2$ = 0.946, D = 방사선조사선량, Gy), $BMD(mg{\cdot}cm^{-3})=8.8115D^2-56.197D+194.41$ ($r^2$ = 0.999, D = 방사선조사선량, Gy) 였다. 뼈의 물리적 강도, 길이 및 무게의 변화는 없었으며, 혈청ALP 농도 및 뼈파괴세포 활성도도 차이가 없었다. 본 연구의 결과는 성장기 동물에서 방사선에 의한 뼈손상 연구에 동물모델 기초자료가 될 수 있을 것이다.

Keywords

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