Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
권호 표지
DOI QR코드

DOI QR Code

The immunosuppression effect of cyclosporine A on the allogenic calvarial bone graft in mice

생쥐 두개골에서 동종골 이식 시 면역억제에 대한 cyclosporine A의 효과

  • Kim, Bang-Sin (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Park, Sang-Mook (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Kim, Kyung-Rak (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Jeoung, Youn-Wook (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Han, Man-Seung (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Kook, Min-Suk (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Park, Hong-Ju (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Ryu, Sun-Youl (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University) ;
  • Oh, Hee-Kyun (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University)
  • 김방신 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 박상묵 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 김경락 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 정연욱 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 한만승 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 국민석 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 박홍주 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 유선열 (전남대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 오희균 (전남대학교 치의학전문대학원 구강악안면외과학교실)
  • Received : 2010.07.05
  • Accepted : 2010.10.22
  • Published : 2010.10.29
Download PDF
⟨ Previous Next ⟩

Abstract

Introduction: This study examined the effect of cyclosporine A (CsA) on the allogenic cranial bone graft in the mice. Materials and Methods: Twenty eight 12-week-old male ICR mice weighing 40 g were used. The experimental group was injected subcutaneously with CsA (10 mg/kg/day) diluted in Caster oil for 7 days prior to the graft until sacrifice. The control group was injected with the same solution without CsA. Two full-thickness bone defects with a diameter of 3 mm were made with a trephine bur in the parietal bone lateral to the sagittal suture. A calvarial defect of a mouse was grafted with allogenic calvarial bone disc from another mouse. The experimental and control groups were injected with CsA and the solution without CsA in the same manner before surgery, respectively. The mice were sacrificed at 1 week, 2 weeks and 4 weeks after the bone graft, respectively. Results: In the experimental group, fibrous connective tissues and small amounts of inflammatory cells were observed. At 2 weeks after the allograft in the experimental group, new bone formation in fibrous collagenous tissue and around the allogenic bone was noted. At 4 weeks after the allograft, new bone formation was active along and at the periphery of the mature allogenic bone. The proliferation of blood vessels increased in bone marrow. In the control group, fibrous tissues and inflammatory cells were observed around the allogenic bone and existing bone at 1 week. At 2 weeks after the allograft, the proliferation of blood vessels accompanied by inflammatory cells were scattered in the fibrous connective tissues. New bone formation around the allogenic and existing bone could be observed. At 4 weeks after the allograft, inflammatory cells were severely infiltrated around the allogenic bone. Osteoclasts were scattered along the allogenic bone and induced bone resorption. Conclusion: These results suggest that the daily administration of CsA (10 mg/kg/day) induces efficient immunosuppression without serious complications, and this protocol might be useful for the experimental model of allogenic bone grafts.

Keywords

References

  1. Yanagihara RH, Adler WH. Inhibition of mouse natural killer activity by cyclosporin A. Immunology 1982;45:325-32.
  2. Wachowiak J. Effects of cyclosporin A on the activity of mouse natural killer cells and hybrid resistance. Immunol Lett 1986;13: 95-9. https://doi.org/10.1016/0165-2478(86)90133-1
  3. Yanagihara RH, Adler WH. Cyclosporin a inhibits T cell-mediated augmentation of mouse natural killer activity. Immunopharmacology 1982;4:243-52. https://doi.org/10.1016/0162-3109(82)90006-6
  4. Nemlander A, Hayry P. Effect of cyclosporin A on the generation of cytotoxic T lymphocytes in mouse mixed lymphocyte culture. Scand J Immunol 1980;12:493-8. https://doi.org/10.1111/j.1365-3083.1980.tb00096.x
  5. Alberti S, Boraschi D, Luini W, Tagliabue A. Effects of in vivo treatments with cyclosporin-A on mouse cell-mediated immune responses. Int J Immunopharmacol 1981;3:357-64. https://doi.org/10.1016/0192-0561(81)90031-X
  6. Friedlaender GE. Immune responses to osteochondral allografts. Current knowledge and future directions. Clin Orthop Relat Res 1983;(174):58-68.
  7. Friedlaender GE. Bone allografts: the biological consequences of immunological events. J Bone Joint Surg Am 1991;73:1119-22.
  8. Horowitz MC, Friedlaender GE. Immunologic aspects of bone transplantation. A rationale for future studies. Orthop Clin North Am 1987;18:227-33.
  9. Horowitz MC, Friedlaender GE. Induction of specific T-cell responsiveness to allogeneic bone. J Bone Joint Surg Am 1991;73: 1157-68.
  10. Stevenson S. The immune response to osteochondral allografts in dogs. J Bone Joint Surg Am 1987;69:573-82.
  11. Stevenson S, Horowitz M. The response to bone allografts. J Bone Joint Surg Am 1992;74:939-50.
  12. Ekelund AL, Nilsson O. Effects of cyclosporin A on bone turnover and on resorption of demineralized bone matrix. Clin Orthop Relat Res 1996;(326):127-34.
  13. Frame JW. A convenient animal model for testing bone substitute materials. J Oral Surg 1980;38:176-80.
  14. Casser-Bette M, Murray AB, Closs EI, Erfle V, Schmidt J. Bone formation by osteoblast-like cells in a three-dimensional cell culture. Calcif Tissue Int 1990;46:46-56. https://doi.org/10.1007/BF02555824
  15. Bhargava U, Bar-Lev M, Bellows CG, Aubin JE. Ultrastructural analysis of bone nodules formed in vitro by isolated fetal rat calvaria cells. Bone 1988;9:155-63. https://doi.org/10.1016/8756-3282(88)90005-1
  16. Nagata T, Bellows CG, Kasugai S, Butler WT, Sodek J. Biosynthesis of bone proteins [SPP-1 (secreted phosphoprotein- 1, osteopontin), BSP (bone sialoprotein) and SPARC (osteonectin)] in association with mineralized-tissue formation by fetal-rat calvarial cells in culture. Biochem J 1991;274:513-20.
  17. Ellis CN, Fradin MS, Messana JM, Brown MD, Siegel MT, Hartley AH, et al. Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. N Engl J Med 1991;324:277-84. https://doi.org/10.1056/NEJM199101313240501
  18. Green CJ. Experimental transplantation and cyclosporine. Transplantation 1988;46(2 Suppl):3S-10S.
  19. Tugwell P, Bombardier C, Gent M, Bennett KJ, Bensen WG, Carette S, et al. Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis. Lancet 1990;335:1051-5. https://doi.org/10.1016/0140-6736(90)92630-Z
  20. Boland J, Atkinson K, Britton K, Darveniza P, Johnson S, Biggs J. Tissue distribution and toxicity of cyclosporin A in the mouse. Pathology 1984;16:117-23. https://doi.org/10.3109/00313028409059087
  21. Shi CL, Rooth P, Taljedal IB. Effects of cyclosporin A and verapamil on mouse pancreatic islets. Acta Endocrinol (Copenh) 1993;129:54-8.
  22. Fabien NH, Auger C, Moreira A, Monier JC. Effects of cyclosporin A on mouse thymus: immunochemical and ultrastructural studies. Thymus 1992;20:153-62.
  23. Aramant R, Turner JE. Cross-species grafting of embryonic mouse and grafting of older postnatal rat retinas into the lesioned adult rat eye: the importance of cyclosporin A for survival. Brain Res 1988;469:303-7.
  24. Lems SP, Capel PJ, Koene RA. Rejection of long-surviving mouse skin allografts after withdrawal of cyclosporin A therapy. Transplant Proc 1980;12:283-6.
  25. Autenried P, Halloran PF. Cyclosporine blocks the induction of class I and class IIMHC products in mouse kidney by graft-vshost disease. J Immunol 1985;135:3922-8.
  26. Halloran PF, Lee EH, Ziv I, Langer F, Gross AE. Orthotopic bone transplantation in mice. II. Studies of the alloantibody response. Transplantation 1979;27:420-6.
  27. Urist MR, Silverman BF, Buring K, Dubuc FL, Rosenberg JM. The bone induction principle. Clin Orthop Relat Res 1967;53: 243-83.