Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
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EXPRESSION OF OSTEOCALCIN AND CALLUS REACTION DURING DISTRACTION OSTEOGENESIS WITH RECOMBINANT HUMAN BONE MORPHOGENIC PROTEIN-7 INJECTION

성견의 골신장술에서 골절단술시 재조합 인간 골형성 단백질-7적용에 따른 가골반응과 Osteocalcin 발현도에 대한 연구

  • Cho, Yeong-Cheol (Department of Oral & Maxillofacial Surgery, College of Medicine, Ulsan University) ;
  • Sung, Iel-Yong (Department of Oral & Maxillofacial Surgery, College of Medicine, Ulsan University) ;
  • Byun, June-Ho (Department of Oral & Maxillofacial Surgery, College of Medicine, Gyeongsang National University) ;
  • Park, Bong-Uk (Department of Oral & Maxillofacial Surgery, College of Medicine, Gyeongsang National University) ;
  • Kim, Uk-Kyu (Department of Oral & Maxillofacial Surgery, College of Dentistry, Busan National University) ;
  • Shin, Sang-Hun (Department of Oral & Maxillofacial Surgery, College of Dentistry, Busan National University) ;
  • Kim, Jong-Ryoul (Department of Oral & Maxillofacial Surgery, College of Dentistry, Busan National University)
  • 조영철 (울산대학병원 구강악안면외과) ;
  • 성일용 (울산대학병원 구강악안면외과) ;
  • 변준호 (경상대학교 구강악안면외과) ;
  • 박봉욱 (경상대학교 구강악안면외과) ;
  • 김욱규 (부산대학교 구강악안면외과) ;
  • 신상훈 (부산대학교 구강악안면외과) ;
  • 김종렬 (부산대학교 구강악안면외과)
  • Published : 2006.08.31
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Abstract

Purpose : The aim of this study was to evaluate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) injected on the rate of new-bone formation for distraction osteogenesis on dogs. Materials & Methods : Twelve adult dogs were randomly selected into two groups of six dogs on each. Unilateral osteotomies were performed on the body of the mandible and an intraoral distractor was mounted to the mandible on dogs. One group was treated with injection of rhBMP-7 and the other group served as the control. RhBMP-7 was administered on the day of surgery by single injection into the medullary bone at the osteotomy gap. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. The animals were then sacrificed at 2, 4, and 8 weeks after completion of the distraction. Two dogs in each group, totaling four dogs, were killed at 2 weeks, 4 weeks, and 8 weeks after completion of distraction, respectively. The lengthened mandibles were harvested and processed for radiographic and histological examinations. In addition, immunohistochemical examination using osteocalcin expression was studied. Results : Radiographs showed accelerated regenerate ossification with maturation of new bone in the rhBMP-7 group comparing with the control group at the 4 weeks of the consolidation. There was no significant difference in the radiographic findings at the 2 weeks and 8 weeks of the consolidation period. Histological findings demonstrated increased bone healing pattern in the rhBMP-7-treated group during all observation period. The expression of osteocalcin immunoreactivity was hardly detected in the normal mandible of dog, but the expression was detected in all experimental rhBMP-7 treated specimens. There were also significant increasing in number of positive immunostaining cells and staining intensity of osteocalcin expression in the rhBMP-7 treated group compared with those of the control group on 2-weeks and 4-weeks. There was a significant decreasing in staining intenstiy of all both two groups on 8 weeks of consolidation period, but significant differences of immunostaining was not seen in two groups. Conclusions : A single injection of rhBMP-7 at the time of osteotomy may stimulate the rate of regenerate ossification and increase callus maturation during distraction osteogenesis. In addition, it may shorten the distraction osteogenesis procedure and decrease the prevalence of complications associated with mandibular distraction osteogenesis.

Keywords

References

  1. Cillo JE Jr, Gassner R, Koepsel RR, Buckley MJ: Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: implications for distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:147-154 https://doi.org/10.1067/moe.2000.107531
  2. Weiss S, Baumgart R, Jochum M, Strasburger CJ, Bidlingmaier M: Systemic regulation of distraction osteogenesis: a cascade of biochemical factors. J Bone Miner Res 2002;17:1280-1289 https://doi.org/10.1359/jbmr.2002.17.7.1280
  3. Mofid MM, Manson PN, Robertson BC, Tufaro AP, Elias JJ, Vander Kolk CA: Craniofacial distraction osteogenesis: a review of 3278 cases. Plast Reconstr Surg 2001;108:1103-1114 https://doi.org/10.1097/00006534-200110000-00001
  4. Wiedemann M: Callus distraction: a new method? A historical review of limb lengthening. Clin Orthop Relat Res 1996;327:291-304 https://doi.org/10.1097/00003086-199606000-00036
  5. Raschke MJ, Bail H, Windhagen HJ, Kolbeck SF, Weiler A, Raun K, Kappelgard A, Skiaerbaek C, Haas NP: Recombinant growth hormone accelerates bone regenerate consolidation in distraction osteogenesis. Bone 1999;24:81-88 https://doi.org/10.1016/S8756-3282(98)00158-6
  6. Yamane K, Okano T, Kishimoto H, Hagino H: Effect of ED-71 on modeling of bone in distraction osteogenesis. Bone 1999;24:187-193 https://doi.org/10.1016/S8756-3282(98)00179-3
  7. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G: Increased bone formation in osteocalcin-deficient mice. Nature 1996;382:448-452 https://doi.org/10.1038/382448a0
  8. Mehrara BJ, Rowe NM, Steinbrech DS, Dudziak ME, Saadeh PB, McCarthy JG, Gittes GK, Longaker MT: Rat mandibular distraction osteogenesis: II. Molecular analysis of transforming growth factor beta-1 and osteocalcin gene expression. Plast Reconstr Surg 1999;103:536-547 https://doi.org/10.1097/00006534-199902000-00026
  9. Windhagen H, Witte F, Hurschler C, Maciejewski O, Linnenberg D, Thorey F: Bone turnover during distraction osteogenesis in an experimental sheep model. Arch Orthop Trauma Surg 2002;122:279-282 https://doi.org/10.1007/s00402-001-0380-5
  10. Mizumoto Y, Moseley T, Drews M, Cooper VN 3rd, Reddi AH: Acceleration of regenerate ossification during distraction osteogenesis with recombinant human bone morphogenetic protein-7. J Bone Joint Surg Am 2003;85:124-130
  11. Ilizarov GA: The tension-stress effect on the genesis and growth of tissues. Part I. The influence of stability of fixation and soft-tissue preservation. Clin Orthop Relat Res 1989;238:249-281
  12. Snyder CC, Levine GA, Swanson HM, Browne EZ Jr: Mandibular lengthening by gradual distraction. Preliminary report. Plast Reconstr Surg 1973;51:506-508 https://doi.org/10.1097/00006534-197305000-00003
  13. Hamanishi C, Yoshii T, Totani Y, Tanaka S: Bone mineral density of lengthened rabbit tibia is enhanced by transplantation of fresh autologous bone marrow cells. An experimental study using dual X-ray absorptiometry. Clin Orthop Relat Res 1994;303:250-255
  14. Pepper JR, Herbert MA, Anderson JR, Bobechko WP: Effect of capacitive coupled electrical stimulation on regenerate bone. J Orthop Res 1996;14:296-302
  15. Tsubota S, Tsuchiya H, Shinokawa Y, Tomita K, Minato H: Transplantation of osteoblast-like cells to the distracted callus in rabbits. J Bone Joint Surg Br 1999;81:125-129 https://doi.org/10.1302/0301-620X.81B1.9018
  16. Wiltfang J, Kessler P, Merten HA, Neukam FW: Continuous and intermittent bone distraction using a microhydraulic cylinder: an experimental study in minipigs. Br J Oral Maxillofac Surg 2001;39:2-7 https://doi.org/10.1054/bjom.2000.0564
  17. Mayr E, Laule A, Suger G, Ruter A, Claes L: Radiographic results of callus distraction aided by pulsed low-intensity ultrasound. J Orthop Trauma 2001;15:407-414 https://doi.org/10.1097/00005131-200108000-00005
  18. Mofid MM, Inoue N, Atabey A, Marti G, Chao EY, Manson PN, Vander Kolk CA: Callus stimulation in distraction osteogenesis. Plast Reconstr Surg 2002;109:1621-1629 https://doi.org/10.1097/00006534-200204150-00020
  19. Croteau S, Rauch F, Silvestri A, Hamdy RC: Bone morphogenetic proteins in orthopedics: from basic science to clinical practice. Orthopedics 1999;22:686-695
  20. Kloen P, Doty SB, Gordon E, Rubel IF, Goumans MJ, Helfet DL: Expression and activation of the BMP-signaling components in human fracture nonunions. J Bone Joint Surg Am 2002;84:1909- 1918 https://doi.org/10.2106/00004623-200211000-00001
  21. Liu F, Ventura F, Doody J, Massague J: Human type II receptor for bone morphogenic proteins(BMPs): extension of the two-kinase receptor model to the BMPs. Mol Cell Biol 1995;15:3479-3486 https://doi.org/10.1128/MCB.15.7.3479
  22. Hogan BL: Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 1996;10:1580-1594 https://doi.org/10.1101/gad.10.13.1580
  23. Yamaguchi A, Ishizuya T, Kintou N, Wada Y, Katagiri T, Wozney JM, Rosen V, Yoshiki S: Effects of BMP-2, BMP-4, and BMP-6 on osteoblastic differentiation of bone marrow-derived stromal cell lines, ST2 and MC3T3-G2/PA6. Biochem Biophys Res Commun 1996;220:366-371 https://doi.org/10.1006/bbrc.1996.0411
  24. Abe E, Yamamoto M, Taguchi Y, Lecka-Czernik B, O'Brien CA, Economides AN, Stahl N, Jilka RL, Manolagas SC: Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res 2000;15:663-673 https://doi.org/10.1359/jbmr.2000.15.4.663
  25. Campisi P, Hamdy RC, Lauzier D, Amako M, Rauch F, Lessard ML: Expression of bone morphogenetic proteins during mandibular distraction osteogenesis. Plast Reconstr Surg 2003;111 :201-208 https://doi.org/10.1097/00006534-200301000-00035
  26. Terheyden H, Wang H, Warnke PH, Springer I, Erxleben A, Ludwig K, Rueger DC: Acceleration of callus maturation using rhOP-1 in mandibular distraction osteogenesis in a rat model. Int J Oral Maxillofac Surg 2003;32:528-533 https://doi.org/10.1016/S0901-5027(03)90408-X
  27. Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H, Tucker RF, White KH, Coughlin JE, Tucker MM, Pang RH: Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem 1992;267:20352-20362
  28. Li G, Bouxsein ML, Luppen C, Li J, Wood M, Seeherman HJ, Wozney JM, Simpson H: Bone consolidation is enhanced by rhBMP- 2 in a rabbit model of distraction osteogenesis. J Orthop Res 2002;20:779-788 https://doi.org/10.1016/S0736-0266(01)00166-8
  29. Boutahar N, Guignandon A, Vico L, Lafage-Proust MH: Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activation. J Biol Chem 2004;279:30588-30599 https://doi.org/10.1074/jbc.M313244200
  30. Yoshikawa T, Peel SA, Gladstone JR, Davies JE: Biochemical analysis of the response in rat bone marrow cell cultures to mechanical stimulation. Biomed Mater Eng 1997;7:369-377
  31. Lawton DM, Andrew JG, Marsh DR, Hoyland JA, Freemont AJ: Expression of the gene encoding the matrix gla protein by mature osteoblasts in human fracture non-unions. Mol Pathol 1999;52:92-96 https://doi.org/10.1136/mp.52.2.92
  32. Mora S, Pitukcheewanont P, Kaufman FR, Nelson JC, Gilsanz V: Biochemical markers of bone turnover and the volume and the density of bone in children at different stages of sexual development. JBone Miner Res 1999;14:1664-1671 https://doi.org/10.1359/jbmr.1999.14.10.1664
  33. Shirakawa Y, Shirahata A, Fukuda M: Differences in reactivity to vitamin K administration of the vitamin K-dependent procoagulant factors, protein C and S, and osteocalcin. Semin Thromb Hemost 2000;26:119-126 https://doi.org/10.1055/s-2000-9814
  34. Desbois C, Karsenty G: Osteocalcin cluster: implications for functional studies. J Cell Biochem 1995;57:379-383 https://doi.org/10.1002/jcb.240570302
  35. Fink B, Fox F, Singer J, Skripitz R, Feldkamp J: Monitoring of bone formation during distraction osteogenesis via osteocalcin: a time sequence study in dogs. J Orthop Sci 2002;7:557-561 https://doi.org/10.1007/s007760200099
  36. Warren SM, Mehrara BJ, Steinbrech DS, Paccione MF, Greenwald JA, Spector JA, Longaker MT: Rat mandibular distraction osteogenesis: part III. Gradual distraction versus acute lengthening. Plast Reconstr Surg 2001;107:441-453 https://doi.org/10.1097/00006534-200102000-00021
  37. Sato M, Yasui N, Nakase T, Kawahata H, Sugimoto M, Hirota S, Kitamura Y, Nomura S, Ochi T: Expression of bone matrix proteins mRNA during distraction osteogenesis. J Bone Miner Res 1998; 13:1221-1231 https://doi.org/10.1359/jbmr.1998.13.8.1221