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신연 골형성술시 신연속도에 따른 골형성 관여 인자의 발현

Expression of osteogenesis related factors according to distraction rate in the distraction osteogenesis

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초록

Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension- stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. The purpose of this study is to examine the pattern of expression of growth factors(TGF-β1, IGF-I, bFGF) and extracellular matrix proteins(osteoclacin, osteonectin) related to osteogenesis by osteodistraction of the mandible in rabbits. 24 rabbits is used for this experiment. Experimental group are gradual distraction(0.7mm, twice/day), acute distraction(1.4mm, twice/day) and control group is only osteotomized. After 5 days latency, osteotomic site is distracted for each 7 days and 3.5 days. Consolidation period is 28 days. The animal is sacrificed at the 3th, 7th, 14th, 28th. The distracted bone is examined by immunohistochemical analysis and RT-PCR analysis. The results obtained from this study were as follow : No significant difference was found on clinical examination according to distraction rate, but gradual distraction was shown to improve regenerate bone formation on radiographic and histologic examination. Growth factors and extracelluar matrix proteins expression increased in distraction group than control group. From these results, it could be stated that graudal distraction is shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteogenesis related factors. And rabbit is the most appropriate animal model for further reseach on the molecular mechanisms that mediate osteodistraction. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.

Abstract

Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension- stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. The purpose of this study is to examine the pattern of expression of growth factors(TGF-β1, IGF-I, bFGF) and extracellular matrix proteins(osteoclacin, osteonectin) related to osteogenesis by osteodistraction of the mandible in rabbits. 24 rabbits is used for this experiment. Experimental group are gradual distraction(0.7mm, twice/day), acute distraction(1.4mm, twice/day) and control group is only osteotomized. After 5 days latency, osteotomic site is distracted for each 7 days and 3.5 days. Consolidation period is 28 days. The animal is sacrificed at the 3th, 7th, 14th, 28th. The distracted bone is examined by immunohistochemical analysis and RT-PCR analysis. The results obtained from this study were as follow : No significant difference was found on clinical examination according to distraction rate, but gradual distraction was shown to improve regenerate bone formation on radiographic and histologic examination. Growth factors and extracelluar matrix proteins expression increased in distraction group than control group. From these results, it could be stated that graudal distraction is shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteogenesis related factors. And rabbit is the most appropriate animal model for further reseach on the molecular mechanisms that mediate osteodistraction. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.

참고문헌 (54)

  1. Ilizarov GA, "A new principle of osteosynthesis with the use of crossing pins and rings. In Collection of Scientific Works of the Kurgan Regional Scientific Medical Society", pp.145~160 (1954), Kurgan, USSR
  2. Codivilla A, "On the means of lengthening in the lower limb, the muscles and tissues which are shortened through deformity", Am J Orthop Surg, 2, pp.353~369 (1905)
  3. Ilizarov GA, "The tension-stress effect on the genesis and growth of tissues: I. The influence of stability of fixation and soft-tissue preservation", Clin Orthop, 238, pp.249~ (1989)
  4. Ilizarov GA, "The tension-stress effect on the genesis and growth of tissues: II. The influence of the rate and frequency of distraction", Clin Orthop, 239, pp.263~ (1989)
  5. Snyder CC, "Mandibular lengthening by gradual distraction", Plast Reconstr Surg, 51, pp.506~508 (1973)
  6. McCarthy JG, "Lengthening the human mandible by gradual distraction", Plast Reconstr Surg, 89, pp.1~10 (1992)
  7. Swennen G, "Craniofacial distraction osteogenesis: a review of the literature. Part I: clinical studies", Int J Oral Maxillofac Surg, 30, pp.89~103 (2001)
  8. Swennen G, "Craniofacial distraction osteogenesis: a review of the literature. Part II: experimental studies", Int J Oral Maxillofac Surg, 31, pp.123~135 (2002)
  9. Rowe NM, "Rat mandibular distraction osteogenesis: Part I. Histologic and radiographic analysis", Plast Reconstr Surg, 102, pp.2022~2032 (1998)
  10. Mehrara BJ, "Rat mandibular distraction osteogenesis: II, Molecular analysis of transforming growth factor beta 1 and osteocalcin gene expression", Plast Reconstr Surg, 103, pp.536~547 (1999)
  11. Warren SM, "Rat mandibular distraction osteogenesis. Part III Gradual distraction versus acute lengthening", Plast Reconstr Surg, 107, pp.441~453 (2001)
  12. 김부경, "백서경골에서 신연속도에 따른 골형성 비교 연구", 대구외지, 26(6), pp.620~627 (2000)
  13. 김기영, "가토에서 하악골 신연 양에 따른 하치조신경의 조직학적 변화", 대악성외지, 20(3), pp.250~255 (1998)
  14. 윤경인, "하악골 신연술후 생성된 신생골의 조직학적 및 면역화학적 소견", 대악성외지, 23(3), pp.258~262 (2001)
  15. 오유근, "구내 신연장치를 이용한 치조골 신연에 미치는 잠복기의 영향", 대악성외지, 23, pp.324~331 (2001)
  16. 정현, "치조골 신연후 임프란트 매식시기에 따른 골유착 효과", 대구외지, 26(3), pp.238~244 (2000)
  17. 김명진, "Callus distraction method를 이용한 하악골 신장술: 계단골절단 술식의 적용", 대악성외지, 22(2), pp.254~261 (2000)
  18. 박영욱, "점진적 Distraction Technique을 이용한 상악골의 전방이동", 대악성외지, 22(6), pp.687~696 (2000)
  19. 김진, "악안면 기형 환자에서 악골 신장술의 적용", 대악성외지, 22(6), pp.657~663 (2000)
  20. 임순모, "성견 하악 골체부 신장시 신장부위의 증식세포핵항원과 제 1형 교원질 발현에 관한 연구", 대구외지, 27(5), pp.385~393 (2001)
  21. 백선호, "성견 하악골 절단 후 기계적 골 견인에 의해 형성된 골 신장부에 대한 시기별 조직학적 변화", 대구외지, 27, pp.404~413 (2001)
  22. 송정호, "백서 하악골에서 신연빈도에 따른 골형성 비교 연구", 대한악안면성형재건외과학회지, 24(2), pp.115~125 (2002), 대한악안면성형재건외과학회
  23. 류수장, "성견 하악골의 신연 부위에서 골형성에 대한 혈소판-풍부 혈장의 효과", 대구외지, 27(6), pp.498~510 (2001)
  24. Sato M, "Expression of bone matrix proteins mRNA during distraction osteogenesis", J Bone Miner Res, 13, pp.1221~1231 (1998)
  25. Sato M, "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, 14, pp.1084~1095 (1999)
  26. Eingartner C, "Growth factors in distraction osteogenesis. Immunohistological pattern of TGF-beta 1, IGF-I in human callus induced by distraction osteogenesis", Int Orthop, 23, pp.253~259 (1999)
  27. Tavakoli K, "Expression of growth factor in the mandiblar distraction zone: a sheep study", Br J Plast Surg, 52, pp.434~439 (1999)
  28. Kojimoto H, "Bone lengthening in rabbits by callus distraction", J Bone Joint Surg(Br), 70B, pp.543~549 (1988)
  29. Yasui N, "Three modes of ossification during distraction osteogenesis in the rat", J Bone Joint Surg Br, 79(5), pp.824~830 (1997)
  30. Ueda M, "Mechanisms of new bone formation during distraction osteogenesis a preliminary report: Samchukov ML, Cope JB, Cherkashin AM Craniofacial Distraction Osteogenesis", pp.37~41 (2001), Mosby
  31. Buckley MJ, "The effects of mechanicl strain on osteoblasts in vitro", J Oral Maxillofac Surg, 48, pp.276~282 (1990)
  32. Burger EH, "Mechanical stress and ostogenesis in vitro", J Bone Miner Res. Suppl, 2, pp.S397~S401 (1992)
  33. Linkhart TA, "Growth factors for bone growth and repair: IGF, TGFb, and BMP", Bone, 19, pp.1S~12S (1996)
  34. Wahl SM, "Transforming growth factor β: the good, the bad, and the ugly", J Exptl Med, 180, pp.1587~1590 (1994)
  35. Yeung HY, "Sustained expression of transforming growth factor-beta1 by distraction during distraction osteogenesis", Life Sci, 24(71(1)), pp.67~79 (2002)
  36. Critchow MA, "The effect of exogenous transforming growth factor-beta 2 on healing fractures in the rabbit", Bone, 16, pp.521~527 (1995)
  37. Rauch F, "Effects of locally applied transforming growth factor-beta 1 on distraction osteogenesis in a rabbit limb-lengthening model", Bone, 26, pp.619~624 (2000)
  38. Rosen CJ, "Insulin-like growth factors and bone: the osteoporosis connection", Proc Soc Exptl Biol Med, 206, pp.83~102 (1994)
  39. Baxter RC, "Insulin-like growth factor(IGF) binding proteins: the role of serum IGFBPs in regulating IGF availability", Acta Paed Scand(Suppl), 372, pp.107~114 (1991)
  40. Lammens J, "Distraction bone healing versus osteotomy healing: A comparative biochemical analysis", J Bone Miner Res, 13, pp.279~286 (1998)
  41. Liu Z, "Molecular signaling in bone fracture healing and distraction osteogenesis", Histol Histopathol, 14, pp.587~595 (1999)
  42. Schumacher B, "Periosteal insulin-like growth factor I and bone formation. Changes during tibial lengthening in rabbits", Acta Orthop Scand, 67, pp.237~241 (1996)
  43. Stewart KJ, "A quantitative analysis of the effect of insulinlike growth factor-1 infusion during mandibular distraction osteogenesis in rabbits", Br J Plast Surg, 52, pp.343~350 (1999)
  44. Bail HJ, "The effect of growth hormone on insulin-like growth factor I and Bone metabolism in distraction osteogenesis", Growth Horm & IGF Res, 11(5), pp.314~323 (2001)
  45. Kimoto T, "Continuous administration of basic fibroblast growth factor(FGF-2) accelerates bone induction on rat calvaria an application of a new drug delivery system", J Dent Res, 77, pp.1965~1969 (1998)
  46. McCarthy TL, "Effects of fibroblast growth factors on deoxyribonucleic acid and collagen synthesis in rat parietal bone cells", Endocrinology, 125, pp.2118~2126 (1989)
  47. Okazaki H, "Stimulation of bone formation by recombinant fibroblast growth factor-2 in callotasis bone lengthening of rabbits", Calcif Tissue Int, 64, pp.542~546 (1999)
  48. Desbois C, "Osteocalcin cluster: implications for functional studies", J Cell Biochem, 57, pp.379~383 (1995)
  49. Hiltunen A, "Regulation of extracellular matrix genes during fracture healing", Clin Orthop, 297, pp.23~27 (1993)
  50. Meyer U, "Decreased expression of osteocalcin and osteonectin in relation to high strains and decreased mineralization in mandibular distraction osteogenesis", J CranioMaxillofac Surg, 27, pp.222~227 (1999)
  51. Perrien DS, "Immunohistochemical study of osteopontin expression during distraction osteogenesis in the rat", J Histochem Cytochem, 50(4), pp.567~574 (2002)
  52. Lanyon LE, "Osteocytes, strain detection, bone modeling and remodeling", Calcif Tissue Int, 53, pp.S102~S106 (1993)
  53. Aarden EM, "Function of osteocytes in bone", J Cell Biochem, 55, pp.287~299 (1994)
  54. Nomura S, "Molecular events caused by mechanical stress in bone", Matrix Biol, 19, pp.91~96 (2000)

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