ddY 마우스를 이용한 골다공증 모델에 대한 비교연구: 난소적출 및 신경절단 모델

A comparative study on the osteoporotic animal models in ddY mouse: ovariectomized and neurectomized models

  • 이형식 (대구한의대학교 한방생명자원학과) ;
  • 홍표원 (대구한의대학교 한방생명자원학과) ;
  • 구세광 (동화약품(주) 중앙연구소 약리독성연구실) ;
  • 이재현 (경북대학교 수의과대학 조직학교실) ;
  • 함태수 (영남대학교 자연자원대학 생물자원학부)
  • Lee, Hyeung-sik (Department of Herbal Biotechnology, Daegu Haany University) ;
  • Hong, Pyo-one (Department of Herbal Biotechnology, Daegu Haany University) ;
  • Ku, Se-kwang (Pharmacology & Toxicology Lab., Central Research Laboratories) ;
  • Lee, Jae-hyun (Department of Histology, College of Veterinary Medicine, Kyungpook National University) ;
  • Ham, Tae-Su (College of Natural Resources, Yeungnam University)
  • 심사 : 2004.09.15
  • 발행 : 2004.12.30

초록

In order to compare the induced time of osteoporosis between ovariectomized and neurectomized models in ddY mice. Experimental groups were divided into Sham, ovariectomized (OVX group) and neurectomized (NX group) group. The changes of body weight, tibia weight and histomorphometry of epiphyseal regions of tibia that were generally used as criteria index in osteoporosis, were evaluated at 2 and 4 weeks after operations with other generally used index-changes of serum osteocalcin. Also, calcium and phosphorus levels in the ash tibia were demonstrated with their ratio (Ca/P ratio). From the result of this study, evidences which reflect osteoporotic states of animals such as decrease of absolute and relative tibia weight, histomorphometrical index of epiphyseal region of tibia including trabecular bone volume %, and calcium and phosphorous contents in tibia, were generally detected from 4 weeks after ovariectomy and 2 weeks after neurectomy with increase of serum osteocalcin levels. In conclusion, it is considered that more rapid and favorable osteoporosis was induced in neurectomized model compared to that of ovariectomized model.

참고문헌

  1. 석봉, 이광희, 곽양수, 이두진, 박윤기, 이승호. 폐경기증상과 양측 난소제거술이 골밀도에 미치는 영향. 대한산부인과학회지. 1994, 37, 2037-2046
  2. 김남현, 최종혁, 이환. 흰쥐의 난소제거후 발생한 골다공증에 대한 홍삼 사포닌의 효능. 대한정형외과학회지. 1995, 30, 808-816
  3. 이환, 박병문, 김남현. 백서의 난소제거후 발생한 골다공증에 대한 Calcitonin, NaF 및 Tamoxifen의 효과. 대한정형외과학회지. 1993, 28, 2273-2280
  4. 하승우. 골다공증의 치료: 골흡수억제제. 경북대학교 내분비-대사내과 골다공증 논문집. 1995, 51-55
  5. 한병권, 박원, 최태환, 신현우, 김선우. 한국인 갱년기 여성의 골밀도 및 호르몬 변화에 대한 연구. 대한내분비학잡지. 1989, 4, 21028
  6. Abadjieva, D. K. and 강성길. 녹용약침 자극이 난소 적출 흰쥐의 지질 및 골대사에 미치는 영향. 대한한의학회지. 1996, 17, 168-177
  7. Bain, S. D., Bailey, M. C., Celino, D. L., Lantry, M. M. and Edwards, M. W. High-dose estrogen inhibits bone resorption and stimulates bone formation in the ovariectomized mouse. J. Bone Miner. Res. 1993, 8, 435-442 https://doi.org/10.1002/jbmr.5650080407
  8. Blanque, R., Cottereaux, C. and Gardner, C. R. Increases in osteocalcin after ovariectomy are amplified by LPS injection: strain differences in bone remodeling. Gen. Pharmacol. 1998, 30, 51-56 https://doi.org/10.1016/S0306-3623(97)00067-0
  9. Bray, G. A. Genetic, hypothalamic and endocrine features of clinical and experimental obesity. Prog. Brain Res. 1992, 93, 333-341 https://doi.org/10.1016/S0079-6123(08)64583-5
  10. Broulik, P. D. Tamoxifen prevents bone loss in ovariectomized mice. Endocr. Regul. 1991, 25, 217-219
  11. Chikazu, D., Shindo, M., Iwasaka, T., Katagiri, M., Manabe, N., Takato, T., Nakamura, K. and Kawaguchi, H. A novel synthetic triazolotriazepine derivative JTT-606 inhibits bone resorption by downregulation of action and production of bone resorptive factors. J. Bone Miner. Res. 2000, 15, 674-682
  12. Durador, E. B., De-Falco, V., Chahade, W. H., Cossermelli, W. and Yoshinari, N. H. Hormonal and biochemical parameters in postmenopausal osteoporosis. Rev. Hosp. Clin. Fac. Med. Sao. Paul. 1997, 52, 60-62
  13. Erben, R. G., Harti, G. and Graf, H. Ovariectomy dose not alter CD4+/CD8+ ratio in peripheral blood Tlymphocytes in the rat. Horm. Metab. Res. 1998, 30, 50-54
  14. Govan, A. D. T., Macfalane, P. S. and Callander, R. Pathology illustrated. p. 818, 2nd ed. Churchill Livingstone, Edinburgh, 1986
  15. Huuskonen, J., Arnala, I., Olkkonen, H. and Alhava, E. Pamidronate increases trabecular bone mineral density in immobilization osteopenia in male rats. Ann. Chir. Gynaecol. 2001, 90, 37-42
  16. Jee, W. S., Mori, S., Li, X. J. and Chan, S. Prostaglandin E2 enhance cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats. Bone. 1990, 11, 253-266
  17. Kalu, D. N. and Chen, C. Ovariectomized murine model of postmenopausal calcium malabsorption. J. Bone Miner. Res. 1999, 14, 593-601
  18. Kodama, Y., Dimai, H. P., Wergedal, J., Sheng, M., Malpe, R., Kutilek, S., Beamer, W., Donahue, L. R., Rosen, C., Baylink, D. J. and Farley, J. Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading. Bone. 1999, 25, 183-190
  19. Kodama, Y., Umemura, Y., Nagasawa, S., Beamer, W. G., Donahue L. R., Rosen, C. R., Baylink, D. J. and Farley, J. R. Exercise and mechanical loadingincrease periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/Hej mice. Calcif. Tissue Int. 2000, 66, 298-306
  20. Kurachi, H., Adachi, H., Ohtsuka, S., Morishige, K.,Amemiya, K., Keno, Y., Shimomura, I., Tokunage, K., Miyake, A. and Matsuzawa, Y. Involvment of epidermal growth factor in including obesity in ovariectomized mice. Am. J. Physiol. 1993, 265, E323-331
  21. Lorden, J. F. and Caudle, A. Behavioral and endocrinological effects of single injections of monosodium glutamate in the mouse. Neurobehav. Toxicol. Teratol. 1986, 8, 509-519
  22. Murakami, H., Nakamura, T., Tsurukami, H., Abe,M., Barbier, A. and Suzuki, K. Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy. J. Bone Miner. Res. 1994, 9, 1355-1364
  23. Nordin, B. E. Calcium and osteoporosis. Nutrition. 1997, 13, 664-686
  24. Notoya, K., Yoshida, K., Tsukuda, R., Taketomi, S. and Tsuda, M. Increase in femoral bone mass by ipriflavone alone and in combination with 1 alphahydroxyvitamin D3 in growing rats with skeletal unloading. Calcif. Tissue Int. 1996, 58, 88-94
  25. Sakai, A., Nishida, S., Okimoto, N., Okazaki, Y., Hirano, T., Norimura, T., Suda, T. and Nakamura, T. Bone marrow cell development and trabecular bone dynamics after ovariectomy in ddY mice. Bone. 1998, 23, 443-451
  26. Sakai, A., Sakata, T., Ikeda, S., Uchida, S., Okazaki,R., Norimura, T., Hori, M. and Nakamura, T. Intermittent administration of human parathyroid hormone (1-34) prevents immobilization-related bone loss by regulating bone marrow capacity for bone cells in ddY mice. J. Bone Miner. Res. 1999, 14, 1691-1699
  27. Sandstedt, J., Tornell, J., Norjavaara, E., Isaksson, O. G. and Ohlsson, C. Elevated levels of growth hormone increase bone mineral content in normal young mice, but not in ovariectomized mice. Endocrinology. 1996, 137, 3368-3374
  28. Tajima, Y. Stansardized nomenclature for inbred strains of mice. Experimental animals in cancer research. Jpn. Cancer Assoc. Gann. Monograph. 1968, 5, 123-128
  29. Tanaka, S., Shimizu, M., Debari, K., Furuya, R., Kawawa, T. and Sasaki, T. Acute effects of ovariectomy on wound healing of alveolar bone after maxillary molar extraction in aged rats. Anat. Rec. 2001, 262, 203-212
  30. Tarvainen, R., Arnala, I., Olkkonen, H., Lappalainen, R., Nevalainen, T. and Alhava, E. Clodronate prevents immobilization osteopenia in rats. Acta. Orthop. Scand. 2001, 65, 643-646
  31. Tuukkanen, J., Jalovaara, P. and Vaananen, K. Calcitonin treatment of immobilization osteoporosis in rats. Acta. Physiol. Scand. 1991, 141, 119-124
  32. Verhaeghe, J., Thomsen, J. S., van Bree, R., van Herck, E., Bouillon, R. and Mosekilde, L. Effects of excercise and disuse on bone remodeling, bone mass, and biomechanical competence in spontaneously diabetic female rats. Bone. 2000, 27, 249-256
  33. Yamamoto, M., Fisher, J. E., Gentile, M., Seedor, J. G., Leu, C. T., Rodan, S. B. and Rodan, G. A. The integrin ligand echistatin prevents bone loss in ovariectomized mice and rats. Endocrinology. 1998, 139, 1411-1419
  34. Yamashita, T., Sekiya, I., Kawaguchi, N., Nashimada, K., Nifuji, A., Nabeshima, Y. I. and Noda, M. Klothodeficent mice are resistant to bone loss induced by unloading due to sciatic neurectomy. J. Endocrinol. 2001, 168, 347-351
  35. Yonezu, H., Ikata, T., Takata, S. and Shibata, A. Effects of sciatic neurectomy on the femur in growing rats: application of peripheral quantitative computed tomography and Fourier transform infrared spectroscopy. J. Bone Miner. Metab. 1999, 17, 259-265
  36. Yoshitake, H., Rittling, S. R., Denhardt, D. T. and Noda, M. Osteoponin-deficient mice are resistant to ovariectomy-induced bone resorption. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 8156-8160
  37. Zeng, Q. Q., Jee, W. S., Bigornia, A. E., King, J. G. Jr., D’Souza, S. M., Li, X. J., Ma, Y. F. and Wechter, W. J. Time response of cancellous and cortical bones to sciatic neurectomy in growing female rats. Bone. 1996, 19, 13-21