치아재식시 골형태형성단백이 치주조직 치유에 미치는 영향

EFFECTS OF BONE MORPHOGENETIC PROTEIN ON THE HEALING OF PERIODONTIUM AFTER TOOTH REPLANTATION OF THE RAT

  • 김지숙 (경희대학교 치과대학 치주과학교실) ;
  • 박준봉 (경희대학교 치과대학 치주과학교실) ;
  • 이만섭 (경희대학교 치과대학 치주과학교실) ;
  • 권영혁 (경희대학교 치과대학 치주과학교실) ;
  • Kim, Ji-Sook (Department of Periodontology, Division of Dentistry, KyungHee University) ;
  • Park, Joon-Bong (Department of Periodontology, Division of Dentistry, KyungHee University) ;
  • Lee, Man-Sup (Department of Periodontology, Division of Dentistry, KyungHee University) ;
  • Kwon, Young-Hyuk (Department of Periodontology, Division of Dentistry, KyungHee University) ;
  • Cho, Kyoo-Sung (Department of Periodontology, College of Dentistry, Yonsei University)
  • 발행 : 2002.09.30

초록

The purpose of this study is to evaluate the influences of the bone morphogenetic protein (BMP) on the healing of periodontal ligament and alveolar bone after replantation of tooth, and to examine the possibility of its clinical application. 45 Sprague Dawley rats weighted about 100 gram were divided into 3 experimental groups by different dose of BMP. All the upper right and left 1st molar were extracted after 5 days feeding of 0.4% ${\beta}$-aminopropionitrile, and right molar were used as experimental group and left molar were used as control group. The root surface of experimental molar were treated with 25,50 and l00ng/ml of human recombinant Bone morphogenetic protein-4 (rh-BMP-4) with micropipet, and 1M Sodium hypochloride were used on control root surface. All the experimental animals were sacrificed as 1, 2, 4, 7 and 14 days after autoreplantation of upper 1st molar into their own position. The maxilla were disected included both side of 1st molar. The collected tissue were processed from demineralization to paraffin embeding as usual procedure, and the specimens were prepared with Hematoxylin-Eosin stain for the light microscopic evaluation. The results of this study were as follows : 1. There was no significant differences between control and experimental site on 1 and 2 days after replantation of tooth. In the case of 4th days, the evidence of tissue regeneration were observed on experimental site to compare the controls. New osteoid were revealed on high concentration of BMP at 7 days after replantation, and it became more obvious at 14 days, 2. The effect of the rh-BMP-4 coated on root surface was revealed slight influences for the prolifertion of cells of periodontium and tissue regeneration as dose-dependent pattern. 3. Bony ankylosis was observed between alveolar bone and root surface due to the remarkable amount of osteoid formation on the 14 days after replantation of root. In the conclusion, it was suggested that topical application of the rhBMP-4 on the root surface has influence on the periodontal ligament and alveolar bone. The application method of BMP on the root should be designed with calculation of proper concentration.

키워드

참고문헌

  1. Pontoriero R., Lindhe, J., Nyman. S., Karring, T., Resenberg, E., and Sanavi, F. : Guided tissue regeneration in degree II furcation- involved mandibular molars. A clinical study. J. Clin. Periodontol., 15: 247-254, 1988 https://doi.org/10.1111/j.1600-051X.1988.tb01578.x
  2. Caffesse, R,G., Smith, B.A., Duff, B., Morrison, E.C., Merril, D., and Becker, W: Class II furcations treated by guided tissue regeneration in human: Case reports. J. Periodontol., 61: 510-514, 1990 https://doi.org/10.1902/jop.1990.61.8.510
  3. Shigeyama Y, D'errico J., Stone R, and Somerman MJ. : Commercially - prepared allo- graft material has biological activity in vitro. J Periodontol 66: 478-487, 1995 https://doi.org/10.1902/jop.1995.66.6.478
  4. Bowers G., Middleton F., Glynn D., and Sharp S., : Hiotologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with prified bovine collagen. J Periodontal 62: 690-702, 1991 https://doi.org/10.1902/jop.1991.62.11.690
  5. Hotz G, and Herr G. : Bone substitute with osteoinductive biomaterials current and future clinical applications. Int J Oral Maxillofac Surg 23: 413-417, 1994 https://doi.org/10.1016/S0901-5027(05)80033-5
  6. Ripamonti D, and Reddi AH: Periodontal regeneraion: potential role of bone morphogenetic proteins. J Periodont Res 29: 225-235, 1994 https://doi.org/10.1111/j.1600-0765.1994.tb01216.x
  7. Cochran D.L., and Wozney J.M. : Biological mediators for periodontal regeneration. Periodontol 2000. 66: 506-10, 1995
  8. Ripamonti D, Heliotis M, Rueger DC, and Sampath TK. Induction of cementogenesis by recombinant human osteogenic protein-1 (hop-1 /bmp-7) in the baboon (Papio ursinus). Arch Oral BioI. 41: 121-26, 1996 https://doi.org/10.1016/0003-9969(95)00110-7
  9. Melcher, A.H. : On the repair of periodontal tissues. J. Periodontol., 47 : 256-260, 1976 https://doi.org/10.1902/jop.1976.47.5.256
  10. Nyman, S., Gottlow, J., Karring, T., and Lindhe, J. :The regenerative potential of the periodontal ligament-An experimental study in the monkey. J.Clin. Periodontol., 9: 257-265, 1982 https://doi.org/10.1111/j.1600-051X.1982.tb02065.x
  11. Nyman. S., Lindhe, J., Karring, T., and Rylander, H. ; New attachment following surgical treatment of human periodontal disease. J. Clin. Periodontol., 9: 290-296, 1982 https://doi.org/10.1111/j.1600-051X.1982.tb02095.x
  12. Aukhil, I., Pettersson, E., and Suggs, C. : Guided Tissue Regeneration-An experimental procedure in beagle dog. J. Periodontol., 57: 727-734, 1986 https://doi.org/10.1902/jop.1986.57.12.727
  13. Egelberg, J. : Regeneration & repair of periodontal tissue. J. Periodont. Res., 22: 233-242, 1987 https://doi.org/10.1111/j.1600-0765.1987.tb01577.x
  14. Pontoriero R., Lmdhe. J., Nyman. S., Karring,T., Resenberg, E., and Sanavi, F. : Guided tissue regeneration in the treatment of furcation defects in mandibular molars. A clinical study of degree III involvements. J. Clin. Periodontol., 16: 170-174, 1989 https://doi.org/10.1111/j.1600-051X.1989.tb01635.x
  15. Pontoriero R., and Lindhe, J., : Guided tissue regeneration in the treatment of degree III furcation defects in maxillary molars. J. Clin. Periodontol., 22: 810-812, 1995 https://doi.org/10.1111/j.1600-051X.1995.tb00265.x
  16. Jovanovic SA, Spiekermann H, and Richter EJ. : Bone regeneration on titanium dental implants with dehisced defect sites. A clinical study. Int J Oral Maxillofac Implants 7: 233-245, 1992
  17. Nevins M. and Mellonig JT. : The advantages of localized ridge augmentation prior to implant placement : A staged event. Int J Periodont Rest Dent 4; 97-111, 1994
  18. Dahlin C, Gottlow J, Lindhe A. and Nyman S. : Healing of maxillary and mandibular bone defects using a membrqne technique. An experimental study in monkeys. Scand J Plast Reconstr Surg 24: 13-19, 1990 https://doi.org/10.3109/02844319009004514
  19. Becker W, Becker BE, Handelsman M, Celletti R, Ochsenbein C, Hardwick R, and Langer B : Bone foramation at dehisced dental implant sites treated with implant augmentaion material : A pilot study in dogs. Int J Periodont Rest Dent 10: 93-102, 1990
  20. Jovanovic SA, Schenk RK, Orsini M, and Kenney EG. : Supracrestal bone formation around dental implants : An experimental dog study. Int J Oral Maxillofac Implants 10: 21-23, 1995
  21. Lee MB : Bone morphogenetic proeins : background and implications for oral reconstruction A review. J Clin Periodontol 24: 355-365, 1997 https://doi.org/10.1111/j.1600-051X.1997.tb00198.x
  22. Giannobile WV, Hemandez RA, Finkelman RD, Ryan S, Kiritsy CP, D'Andrea M, and Lynch SE. Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individually and in combination on periodontal regeneration in Macaca fascicularis. J Periodontal Res. 31: 301-12,1996 https://doi.org/10.1111/j.1600-0765.1996.tb00497.x
  23. Ripamonti U, and Reddi AH. Tissue engineering, morphogenesis, and regeneration of the periodontal tissues by bone morphogenetic proteins. Crit Rev Oral BioI 8: 154-63, 1997 https://doi.org/10.1177/10454411970080020401
  24. Terranova VP, Franzetti LC, Hic S, and Wikesjo UM. Biochemically mediated periodontal regeneration. J Periodontal Res 22: 248- 51, 1987 https://doi.org/10.1111/j.1600-0765.1987.tb01580.x
  25. Urist MR, Iwata H. and Ceoccotti PL, : Bone morphogenesis in implants of insoluble bone gelatin. Proc Natl Acad Sci(USA) 70: 3511- 3515, 1973 https://doi.org/10.1073/pnas.70.12.3511
  26. Ripamonti, U., Ma, S.S., Cunningham, N.S., Yeates, L., and Reddi, A.H. : Reconstrution of the bone-bone marrow organ by osteogenin, a bone morphogenic protein, and demineralized bone matrix in calvarial defects of adults primates. Plast, Reconstr Surg., 91: 27-36, 1993 https://doi.org/10.1097/00006534-199301000-00005
  27. Sigurdsson TJ, Lee MB, Kubota K, Turek TJ, Wozney JM, and Wikesjo UM. : Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. J. Periodontol. 66: 131-8, 1995 https://doi.org/10.1902/jop.1995.66.2.131
  28. Wozney, J.M : The Potential role of bone morphogenetic protein in periodontal reconstruction. J. Periodontol, 66: 506-510, 1995 https://doi.org/10.1902/jop.1995.66.6.506
  29. Urist, M.R. and Strates, B.S. : Bone morphogenetic protein. J. Dent. Res., 1392-1406, 1971
  30. Urist, M.R., Hue, Y.K., and Brownell, A.G.: Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography. Proc, Natl. Sci. USA, 81: 371-375, 1984 https://doi.org/10.1073/pnas.81.2.371
  31. Wozney, J.M. : Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment. J Clin Periodontol, 26: 392-400, 1999 https://doi.org/10.1034/j.1600-051X.1999.260610.x
  32. Froum, S.J., and Gomez, C. : Periodontal regeneration. Current Opinion periodontol., 1 : 111-128, 1993
  33. Page, R.C. : Periodontal therapy: Prospects for the future. J. Periodontol., 64: 744-753, 1993 https://doi.org/10.1902/jop.1993.64.8s.744
  34. Nygaard-Ostby, P, Tellefsen, G., Sigurdsson, T.J., Zimmerman. G.J., and Wikesjo, U.M.E : Periodontal healing following reconstructive surgery effect of guided tissue regeneration. J. Clin. Periodontol., 23: 1073-1079, 1996 https://doi.org/10.1111/j.1600-051X.1996.tb01806.x
  35. Takiguchi T, Kobayashi M, Suzuki R, Yamaguchi A, Istsu K, Nishihara T, Nagumo M, and Hasegawa K. : Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone celIs isolated from rnandibulae, J Periodontal Res. 33: 476-85, 1998 https://doi.org/10.1111/j.1600-0765.1998.tb02347.x
  36. Thies, R,S., Bauduy, M., Ashton, B.A, Kurtzberg, L., Wozney, J.M., and Rosen, VG : Recombinant human bone morhphogenic protein 2 indueces osteoblastic differentiation in W-2017 stromal cell. Endocrinology, 130: 1318-1324, 1992 https://doi.org/10.1210/en.130.3.1318
  37. Howell TH, FioreIIini J, Jones A, Alder M, Nummikoski P, Lazaro M, Lilly I, and Cochran D. : A feasibility study evaluating rhBMP-2/ absorbable collagen sponge device for local alveolar ridge preservation or augmentation. Int J Periodontics Restorative Dent. 17: 124-39, 1997
  38. Soda H, Raymond E, Sharma S, Laurence R, Cerna C, and Gomez L, : Antiproliferative effects of recombinant human bone morpho- genetic protein-2 on human tumor colony - forming units. Anticancer Drugs 9: 327-331, 1998 https://doi.org/10.1097/00001813-199804000-00006
  39. Ripamonti, R., and Red, A.H. : Periodontal regeneration : Potential role of bone morphogenetic proteins. J. Periodont. Res., 29 : 225-235, 1994 https://doi.org/10.1111/j.1600-0765.1994.tb01216.x
  40. Shigeyama, Y., D'Errico, J.A., Stone, R., and Somerman, M.J. : Commercially-prepared allograft material has biological activity in vitro. J. Periodontol., 66 : 478-487, 1995 https://doi.org/10.1902/jop.1995.66.6.478
  41. Womey, J. M, : The potential role of bone morphogenetic protein in periodontal reconstruction, J. Periodontol., 66 : 506-510, 1995 https://doi.org/10.1902/jop.1995.66.6.506
  42. Riley, E,H., Lane, J.M., Urist, M.R., Lyons, K.M., and Lieberman, J.R. : Bone morphogene- tic protein-2 : Biology and application. Clin. Ortho, Rel. Res., 324 : 39-46, 1996 https://doi.org/10.1097/00003086-199603000-00006
  43. Wozney, J., and Rosen, V. : Bone morphogenetic proteins and bone morphogenetic protein gene family in bone formation and repair. Clin, Ortho. ReI. Res., 346 : 26-37, 1998
  44. Sigurdsson, T,L., Tatakis, D.N., Lee, M.B., and Wikesjo, U.M.E. : Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenic proteins. J. Periodontol., 66: 511-521, 1995 https://doi.org/10.1902/jop.1995.66.6.511
  45. Gould, T.R.L., Melcher, A.H., and Brunette, D.M.: Locationof progenitor cells in periodontal ligament of mouse molar stimulation by wounding. Anat. Rec., 188: 133-142, 1972 https://doi.org/10.1002/ar.1091880202
  46. Gould, T.R,L., Melcher, A,H., and Brunette, D,M.: Migration and division of progenitor cell populations in periodontal ligament after wounding. J. Periodont, Res., 15; 20-42, 1980 https://doi.org/10.1111/j.1600-0765.1980.tb00258.x
  47. McCulloch, C.A.G., and Melcher, A.H. : Cell density and cell generation in the periodontal ligament of mice. Am. J. Anat., 167: 43-58, 1983a https://doi.org/10.1002/aja.1001670105
  48. McCulloch, C.A.G., and Melcher, A.H. : Cell density and cell generation in the periodontal ligament of mice. J. Periodont, Res. 18: 339-352, 1983b https://doi.org/10.1111/j.1600-0765.1983.tb00369.x
  49. McCulloch, C.A.G., Nemeth E., Lowenberg, B., and Melcher, A.H. : Paravascular cells in endosteal spaces of alveolar bone contribute to periodontal ligament cell populations. Anat, Rec., 219: 234-242, 1987
  50. Melcher, A.H. : On the potential of periodontal tissue. J. Periodontol., 47: 50-55, 1976 https://doi.org/10.1902/jop.1976.47.1.50
  51. Higuchi T, Kinoshita A, Takahashi K, Oda S, and Ishikawa I. : Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling. J. Periodontal. 70: 1026-31, 1997 https://doi.org/10.1902/jop.1999.70.9.1026
  52. Howell, T.H., Martuscelli, G., and Oringer, R.J. : Polypeptide growth factors for periodontal regeneration. Current Opinion in Periodontol, 3: 149-156, 1996
  53. Terranova, V.P, and Wikesjo, U.M.E : Ex- tracellular matrices and polypeptide growth factors as mediators of funtions of cells of the peroiodontium. J. Periodontol., 58: 371-380, 1987 https://doi.org/10.1902/jop.1987.58.6.371
  54. Zaman KU, Sugaya T, and Kato H. Effect of recombinant human plate1et-derived growth factor- BB and bone morphogenetic protein-2 application to demineralized dentin on early periodontal ligament cell response. J Periodontal Res. 34: 244-50, 1999 https://doi.org/10.1111/j.1600-0765.1999.tb02250.x
  55. Chen,D., Harris, M.A., Rossini, G., Dunstan, C.R., Dallas, S.L., Feng,J. Q., Munry, G.R., and Harris, S.E. : Bone morphogenetic protein-2 (BMP-2) enhances BMP-3, BMPO-4, and bone cell differentiation marker gene expression suring the induction of mineralized bone matix formation in cultures of feral rat calvarial osteoblasts. Calcof. Tissue Int., 60: 283-290, 1997 https://doi.org/10.1007/s002239900230
  56. Chen P, Carrington JL, Hammonds RG, and Reddi AH.: Stimulation of chondrogenesis in limb bud mesoderm cells by recombinant human bone morphogenetic protein 2B (BMP2B) and modulation by transforming growth factor $\beta1$$\beta2$ https://doi.org/10.1016/0014-4827(91)90403-H
  57. 조성훈, 권영혁, 이만섭, 허 익: 골형태형성단백질 및 상피성장인자가 치주조직재생에 미치는영향. 대한치주과학회지 30(3) 505-515, 2002
  58. Toriumi, D,M., Kotler, G.S., Luxenberg, D.P., Holtrop, M.E., and Wang, E.A. : Mandibular reconstruction with a recombinant bone-inducing factor. Functional, histologic, and biomechanical evaluation. Arch. Otolaryngol. Head Neck Surg, 117: 1101-1112, 1991 https://doi.org/10.1001/archotol.1991.01870220049009
  59. Barboza EP, Duarte ME, Geolas I, Sorensen RG, Riedel GE, and Wikesjo UM. : Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog. J Periodontol. 71: 488-96, 2000 https://doi.org/10.1902/jop.2000.71.3.488
  60. 최진근, 이만섭, 권영혁, 박준봉, 허익 : 골형태형성단백질이 백서치주인대 세포와 두 개관세포에 미치는 영향. 대한치주과학회지, 29(4) 765-784, 1999
  61. Takuwa, Y., Ohse, C., Wang, E.A., Wozney, J.M., and Yamashita, K. : Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblasts cells, MC3T3-E1. Biochem. Biophys. Res. Commun., 174: 96-101, 1991 https://doi.org/10.1016/0006-291X(91)90490-X
  62. Kobayashi M, Takiguchi T, Suzuki R, Yamaguchi A, Deguchi K, Shionome M, Miyazawa Y, Nishihara T, Nagumo M, and Hasegawa K. : Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament. J Dent Res. 78: 1624-33, 1999 https://doi.org/10.1177/00220345990780100701
  63. Wikesjo, U.M.E., Gugielmoni, P., Promsudthi, A., Cho, K.S., Trombelli, L., Selvig, K.A., Jin, L., and Wozney, J.M. : Periodontal repair in dogs: effects of rhBMP-2 concentration of alveolar bone and periodontal attachment. J. Clin, Periodontol., 26: 392-400, 1999 https://doi.org/10.1034/j.1600-051X.1999.260610.x
  64. Wang EA, Rosen V, and D'Alessandro JS, : Recombinant human bone morphogenetic protein induces bone formation, Proc Natl Acad Sci(USA) 87: 2220-2224., 1990 https://doi.org/10.1073/pnas.87.6.2220
  65. Kuboki Y, Sasaki M, Saito A, Takita H, and Kato H. : Regeneration of periodontal ligament and cementum by BMP-applied tissue enginee-ring. Eur J Oral Sci. 106: 197-203, 1998 https://doi.org/10.1111/j.1600-0722.1998.tb02176.x
  66. King GN, King N, and Hughes FJ. : The effect of root surface demineralization on bone morphogenetic protein-2 application to demineralized dentin on early periodontal ligament cell response.J Periodontol, 69: 561-70, 1998 https://doi.org/10.1902/jop.1998.69.5.561
  67. Rutherford, R.B., Sampath,T.K., Rueger, D.C., and Taylor, T.D. : Use of bovine osteogenic protein to promote rapid osseointegration of endosseous dental implants. Int. J. Oral Maxillofac. Implants, 7: 297-301, 1992
  68. Kinoshita, A., Oda, S., takahashi, K., Yokota,S., and Ishikawa, I. : Periodontal regeneration by application of recombinant human bone morphogenetic protein-2 to horizontal circumferential defects created by experimental periodontitis in beagle dogs. J. Periodontol., 68: 103-109, 1997 https://doi.org/10.1902/jop.1997.68.2.103
  69. Giannoble, W.V., Ryan, S., Shih, M.S., Su, D.L., Kaplan, P.L., and Chan, T.C.K. : Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class III furcation defects. J. Periodontol., 69: 129-137, 1998 https://doi.org/10.1902/jop.1998.69.2.129
  70. Wang X, Jin Y, Liu B, Zhou S, Yang L, Xi y, and White FH. : Tissue reactions to titanium implants containing bovine bone morphogenetic protein: a scanning electron microscopic inves- tigation. Int J Oral Maxillofac Surg 23: 115-119, 1994 https://doi.org/10.1016/S0901-5027(05)80605-8
  71. Miki T, Harada K, Imai Y, and Enomoto S. : Effect of freeze-dried poly-L-lactic acid discs mixed with bone morphogenetic protein on the healing of rat skull defects. J Oral Maxillofac Surg 52: 387-391, 1994 https://doi.org/10.1016/0278-2391(94)90443-X
  72. Cho, M.I., Matsuda, N., Ramakrishnan, P.R., Lin, W.L., and Genco, R.J. : Differantal regula- tion of periodontal ligamental cell activities by platelet-derived growth factoer, insulin-like growth factor I and epidermal growth factor. Molecular pthogenesis of periodontal disease. Genco et al Ed. Am. Society for MIcrobioloigy, Washington DC 20005, pp403-414, 1994
  73. Cho, M.I., Mastuda, N., Lin, W.L., Moshier, A., and Ramakrishnan, P.R. : In vitro formation of mineralized nodules by periodontal ligament cell from the rat. Calcif Tissue Int 50: 459-467, 1992 https://doi.org/10.1007/BF00296778
  74. Mukai, M., Yoshimine, Y., Akamine, A., and Maeda, K. : Bone-like nodules formed in vitro by rat periodontal ligament cells. Calci, Tissue. Res., 271: 453-460, 1993 https://doi.org/10.1007/BF02913727
  75. Matsuda, N., Lin, W.L., Kumar, N.M., Cho, M.I., and Genco, R.J, : Mitogenicm chemotactic & synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth facters if Vitro, J. Periodontol, 63: 515-525, 1992 https://doi.org/10.1902/jop.1992.63.6.515