가토 하악골체부 신연 골형성술시 하이알우론산이 세포외 기질 단백질의 발현과 골형성에 미치는 영향

THE EFFECT OF HYALURONIC ACID ON EXPRESSION OF EXTRACELLULAR MATRIX PROTEINS AND BONE FORMATION IN RABBIT MANDIBULAR DISTRACTION OSTEOGENESIS

  • 박기남 (가톨릭대학교 성빈센트병원 치과 구강악안면외과) ;
  • 송현철 (가톨릭대학교 성빈센트병원 치과 구강악안면외과) ;
  • 지유진 (가톨릭대학교 성빈센트병원 치과 구강악안면외과) ;
  • 유진영 (가톨릭대학교 성빈센트병원 임상병리과)
  • Park, Ki-Nam (Div. of OMFS, Dept. of Dentistry, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Song, Hyun-Chul (Div. of OMFS, Dept. of Dentistry, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Jee, Yu-Jin (Div. of OMFS, Dept. of Dentistry, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Yoo, Jin-Young (Dept. of pathology, St. Vincent's Hospital, The Catholic University of Korea)
  • 발행 : 2005.04.30

초록

Distraction osteogenesis is a new bone formation technique. There is a advantage of the environmental adaptation when distraction force is applied to the gap between osteotomy lines. But it has a disadvantage of long-term wearing of the appliance and long consolidation period. Therefore we make an effort to reduce it and repair normal function. Extracellular matrix proteins have a function to control the cellular growth, migration, shape and metabolism. In these, hyaluronic acid is a member of polysaccharide glycosaminoglycans (GAGs) and has a important function as bone formation and osteoinduction property. Purpose : In this experimental study in rabbit mandibular distraction osteogenesis, we investigated the bone enhancing property of hyaluronic acid and the expression of extracellular proteins such as osteocalcin and osteonectin. Materials and Methods : The experimental study was carried out on 24 Korean male white rabbits (both mandibular body, n=48). Distraction group was divided to distraction experimental (A, n=16) and distraction control (B, n=16) by the application of hyaluronic acid (Hyruan, LGCI, Seoul, Korea). Normal control group (C, n=16) was only osteotomized. After 5 days latency, distraction devices were activated at a rate of 1.4 mm per day (0.7 mm every 12hours) for 3.5 days. Animals were sacrificed at postoperative 3, 7, 14, and 28 days. H&E stain and immunohistochemical stain was done on decalcified section. Additionally RT-PCR analysis was done for the identification of the expression of osteocalcin and osteonectin. Results : The bone formation in distraction experimental group was much more than that in distraction and normal control group at postoperative 28 days. In immunohistochemical stain, osteocalcin was enhanced at only postoperative 14 days, but osteonectin was not different at each post-operation days. In RT-PCR analysis, osteocalcin was not different at each post-operation days, but osteonectin was strongly expressed in distraction experimental group at postoperative 7 days. The expression of osteocalcin and osteonectin was elevated during the healing period. Conclusion : We found the good bone formation ability of hyaluronic acid in distraction osteogenesis through the immunohistochemistry and RTPCR analysis to osteocalcin and osteonectin, known as a bone formation marker. The application of hyaluronic acid in distraction osteogenesis is a method to reduce the consolidation period.

키워드

참고문헌

  1. Schendel SA, Epker BN: Result after mandibular advancement surgery: an analysis of 87 cases. J Oral Surg 1980;38:265-282
  2. Cope JB, Samchukov ML, Cherkashin AM: Mandibular distraction osteogenesis: A historic perspective and future directions. Am J Orthod Dentofacial Orthop 1999;115:448-460 https://doi.org/10.1016/S0889-5406(99)70266-0
  3. 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 Rel Res 1989;238:249-281
  4. Snyder CC, Levine GA, Swanson HM, Browne EZ: Mandibular lengthening by gradual distraction. Plast Reconstr Surg 1973;51:506- 508 https://doi.org/10.1097/00006534-197305000-00003
  5. McCarthy JG, Schreiber J, Karp NS, Thorne CH, Grayson BH: Lengthening the human mandible by gradual distraction. Plast Reconstr Sug 1992;89:1-10 https://doi.org/10.1097/00006534-199289010-00001
  6. Cho BC, Park JW, Baik BS, Kwon IC, Kim IS: The role of hyaluronic acid, chitosan, and calcium sulfate and their combined effect on early bony consolidation in distraction osteogenesis of a canine model. J Craniofac Surg 2002;13:783-793 https://doi.org/10.1097/00001665-200211000-00014
  7. Weinzweig J, Baker SB, Mackay GJ, Whitaker LA, Bartlett SP: Immediate versus delayed midface distraction in a primate model using a new intraoral internal device. Plast Reconstr Surg 2002;109: 1600-1610 https://doi.org/10.1097/00006534-200204150-00018
  8. Ilizarov GA: The tension-stress effect on the genesis and growth of tissues: part II, the influence of the rate and frequency of distraction. Clin Orthop Rel Res 1989;239:263-285
  9. Ilizarov GA: Clinical application of the tension-stress effect for limb lengthening. Clin Orthop Rel Res 1990;250:8-26
  10. Costantino PD, Shybut G, Fiedeman CD, Pelzer HJ, Masini M, Shindo ML, Sisson GA Sr: Segmental mandibular regeneration by distraction osteogenesis. An experimental study. Arch Otolaryngol Head Neck Surg 1990;116:535-545 https://doi.org/10.1001/archotol.1990.01870050035003
  11. Karp NS, Thorne CHM, McCarthy JG: Bone lengthening in the craniofacial skeleton. Ann Plastic Surg 1990;24:231-237 https://doi.org/10.1097/00000637-199003000-00007
  12. Mehrara BJ, Rowe NM, Steinbrech DS, Dudziak ME, Saadeh PB, McCarthy JG: Rat mandibular distraction osteogenesis: Part II. Molecular analysis of transforming growth factor beta1 and osteocalcin gene expression. Plast Reconstr Surg 1999;103:536-547 https://doi.org/10.1097/00006534-199902000-00026
  13. Sato M, Ochi T, Nakase T, Hirota S, Kitamura Y, Nomura S et al: Mechanical tension-stress induces expression of bone morphogenetic protein(BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis. J Bone Miner Res 1999;14: 1084-1095 https://doi.org/10.1359/jbmr.1999.14.7.1084
  14. Sato M, Yasui N, Nakase T, Kawahata H, Sugimoto M, Hirota S et al: 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
  15. Meyer U, Meyer T, Vosshans J, Joos U: Decreased expression of osteocalcin and osteonectin in relation to high strains and decreased mineralization in mandibular distraction osteogenesis. J Cranio- Maxillofac Surg 1999;27:222-227 https://doi.org/10.1016/S1010-5182(99)80033-X
  16. Toole BP, Jackson G, Gross J: Hyaluronate in morphogenesis in vitro. Proc Natl Acad Sci USA 1972;69:1384-1386
  17. Toole BP: Hyaluronate and hyaluronidase in morphogenesis and differentiation. Am Zool 1973;13:1061-1065 https://doi.org/10.1093/icb/13.4.1061
  18. Toole BP: Proteoglycans and hyaluronan in morphogenesis and differentiation. In : Hay ED(ed) Cell biology of extracellular matrix. New York, Plenum Press, 1991
  19. Yanagashita M: Function of proteoglycans in extracellular matrix. Acta Pathol Jpn 1993;43:283-293
  20. Fink B, Neuen-Jacob E, Lehmann J, Francke A, Ruther W: Changes in canine peripheral nerves during experimental callus distraction. Clin Orthop 2000;376:252-267 https://doi.org/10.1097/00003086-200007000-00034
  21. Castano FJ, Troulis MJ, Glowacki J, Kaban LB, Yates KE: Proliferation of masseter myocytes after distraction osteogenesis of the porcine mandible. J Oral Maxillofac Surg 2001;59:302-307 https://doi.org/10.1053/joms.2001.21000
  22. Hayatsu K, De Deyne PG: Muscle adaptation during distraction osteogenesis in skeletally immature and mature rabbits. J Orthop Res 2001;19:897-905 https://doi.org/10.1016/S0736-0266(01)00002-X
  23. Kruse-Losler B, Meyer U, Floren C, Joos U: Influence of distraction rates on the temporomandibular joint position and cartilage morphology in a rabbit model of mandibular lengthening. J Oral Maxillofac Surg 2001;59:1452-1459 https://doi.org/10.1053/joms.2001.28281
  24. Meyer K, Palmer JW: The polysaccharide of the vitreous humor. J Biol Chem 1934;107:629-634
  25. Maurer PH, Hudack SS: The isolation of hyaluronic acid from callus tissue of early healing. Arch Biochem Biophys 1952;38:49-53 https://doi.org/10.1016/0003-9861(52)90008-8
  26. Iwata H, Urist MR: Hyaluronic acid production and removal during bone morphogenesis in implants of bone matrix in rats. Clin Orthop Rel Res 1973;90:236-245
  27. Sasaki T, Watanabe C: Stimulation of osteoinduction in bone wound healing by high molecular hyaluronic acid. Bone 1995;16:9-15 https://doi.org/10.1016/S8756-3282(94)00001-8
  28. Pilloni A, Bernard GW: The effect of hyaluronan on mouse intramembranous osteogenesis in vitro. Cell Tissue Res 1998;294: 323-333 https://doi.org/10.1007/s004410051182
  29. Liu SS, Thompson AY, Heidaran MA, Poser JW, Spiro RC: An osteoconductive collagen / hyaluronate matrix for bone regeneration. Biomaterials 1999;20:1097-1108 https://doi.org/10.1016/S0142-9612(99)00006-X
  30. Radice M, Brun P, Cortivo R, Scapinelli R, Battaliard C, Abatangelo G: Hyaluronan-based biopolymers as delivery vehicles for bone marrow derived mesenchymal progenitors. J Biomed Mater Res 2000;50 :101-109 https://doi.org/10.1002/(SICI)1097-4636(200005)50:2<101::AID-JBM2>3.0.CO;2-M
  31. Lisignoli G, Zini N, Remiddi G, Piacentini A, Puggioli A, Trimarchi C, Fini M, Maraldi NM, Facchini A: Basic fibroblast growth factor enhances in vitro mineralization of rat bone marrow stromal cells grown on non-woven hyaluronic acid based polymer scaffold. Biomaterials 2001;22:2095-2105 https://doi.org/10.1016/S0142-9612(00)00398-7
  32. 조용민, 민승기, 김수남, 유용욱: 히알루론산이 골 형성에 미치는 영향에 관한 실험적 연구. 대한구강악안면외과학회지 2002;28: 216-225
  33. Hunt DR, Jovanovic SA, Wikesjo UME, Wozney JM, Bernard GW: Hyaluronan supports recombinat human bone morphogenetic protein- 2 induced bone reconstruction of advanced alvelolar ridge defects in dogs. A pilot study. J Periodontol 2001;72:651-658 https://doi.org/10.1902/jop.2001.72.5.651
  34. Califano L, Cortese A, Zupi A, Tajana G: Mandibular lengthening by externall distraction: an experimental study in the rabbit. J Oral Maxillofac Surg 1994;52:1179-1183 https://doi.org/10.1016/0278-2391(94)90540-1
  35. Desbois C, Karsenty G: Osteocalcin cluster. Implications for functional studies. J Cell Biochem 1995;57:379-383 https://doi.org/10.1002/jcb.240570302
  36. Hiltunen A, Aro HT, Vuorio E: Regulation of extracellular matrix genes during fracture healing in mice. Clin Orthop Rel Res 1993;297 :23-27
  37. Hirakawa K, Hirota S, Ikeda T, Yamaguchi A, Takemura T, Nagoshi J, Yoshiki S, Suda T, Kitamura Y, Nomura S: Localization of the mRNA for bone matrix proteins during fracture healing as determined by in situ hybridization. J Bone Miner Res 1994;9:1551-1557 https://doi.org/10.1002/jbmr.5650091007
  38. Komuro Y, Takato T, Harii K, Yonemara Y: The histologic analysis of distraction osteogenesis of the mandible in rabbits. Plast Reconstr Surg 1994;94:152-159 https://doi.org/10.1097/00006534-199407000-00017
  39. Yasui N, Sato M, Ochi T, Kimura T, Kawahata H, Kitamura Y, Nomura S: Three modes of ossification during distraction osteogenesis in the rat. J Bone Joint Surg Br. 1997;79:824-830 https://doi.org/10.1302/0301-620X.79B5.7423
  40. Knudson CB, Toole BP: Changes in the pericellular matrix during differentiation of limb bud mesoderm. Dev Biol 1985;112:308-318 https://doi.org/10.1016/0012-1606(85)90401-4
  41. Boskey AL, Maresca M, Wikstrom B, Hjerpe A: Hydroxyapatite formation in the presence of proteoglycans of reduced sulfate content: studies in the brachymorphic mouse. Calcif Tissue Int 1991;49:389-393 https://doi.org/10.1007/BF02555848
  42. Baier Leach J, Bivens KA, Patrick Jr CW, Schmidt CE: Photocrosslinked hyaluronic acid hydrogels : Natural, Biodegradable tissue engineering scaffolds. Biotechnol Bioeng 2003;82:578-589 https://doi.org/10.1002/bit.10605