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EXPRESSION OF BMP-2, -4 DURING DISTRACTION OSTEOGENESIS IN THE RABBIT MANDIBLE  

Kim, Sang-Woo (Department of Oral & Maxillofacial Surgery, Graduate School of Clinical Dental Science, The Catholic University of Korea)
Jee, Yu-Jin (Division of Oral & Maxillofacial Surgery, Department of Dentistry, St. Vincent's Hosptital, The Catholic University of Korea)
Song, Hyun-Chul (Division of Oral & Maxillofacial Surgery, Department of Dentistry, St. Vincent's Hosptital, The Catholic University of Korea)
Publication Information
Journal of the Korean Association of Oral and Maxillofacial Surgeons / v.30, no.3, 2004 , pp. 193-202 More about this Journal
Abstract
Distraction osteogenesis(DO) is defined as a gradual mechanical process of mechanical stretching two vascularized bone surface apart with a critical rate and rhythm such that new bone forms within the expanding gap, reliably bridges the gap, and ultimately remodels to normal structure. DO has become a mainstay in bone tissue engineering and has significantly improved our armamentarium for reconstructive craniomaxillofacial procedures. But the molecular and biological mechanisms that regulate the formation of new bone during distraction osteogenesis are not completely understood. BMPs are potent osteoinductive agents. Our hypothesis was that BMPs, especially BMP-2 and BMP-4, might play an importent role in the signaling pathways that link the mechanical forces created by distraction to biological responses and in promting new bone formation. Using a rabbit's mandible, we investigated the expression of BMP-2, -4 at different time points during distraction osteogenesis. The purpose of this study is to research the pattern of expression of BMP-2, -4 in new bone formation during distraction osteogenesis of the rabbit mandible. The experimental group was applied gradual distraction (0.7mm a day by twice a day, 4.9mm in total, for 7 days) and the control group was carried out osteotomy alone. They were examined clinically, histologically, and by RT-PCR analysis. On 3 days after osteotomy, the high level of expression of BMP-2, -4 was detected. But, the expression of BMP-4 was decreased during latency period. As distraction was started, its expression was increased and maintained till postoperative 28days. In control group, the expression of BMP-4was remarkably decreased till postoperative 14 days. On the other hand, the expression of BMP-2 was no difference between experimental group and control group. The expression of BMP-4 was maintanined at high level during the entire experimental period in both group. These findings suggested that excellent bone formation during distraction osteogenesis is associated with enhanced expression of BMP-4 genes by mechanical tension stress.
Keywords
Distraction osteogenesis; Molecular mechanism; RT-PCR analysis; BMP-2; BMP-4;
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Times Cited By KSCI : 1  (Citation Analysis)
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1 Aronson J, Harrison B, Boyd CM, Cannon DJ, Lubansky HJ: Mechanical induction of osteogenesis; the importance of pin rigidity. J Ped Orthop 1988;8:396-401   DOI
2 Bouletreau PJ, Warren SM, Longaker MT: The molecular biology of distraction osteogenesis. J Craniomaxillofac Surg 2002;30:1-11   DOI   PUBMED   ScienceOn
3 Urist MR: Bone Formation by autoinduction. Science 1965;150:893-899   DOI   PUBMED   ScienceOn
4 Leslie CL, Sterling SR, Gilbert T: Recombinant Human Bone BMP-2 for Maxillary Sinus Grafting; 상악동이식술, 정원사, 1999;159-170
5 Rosen V, Cox K, Hattersley G: Bone morphogenetic proteins. In; Bilezikian JP, Raisz LG, Rodan GA. Principles of Bone Biology. Academic Press, Inc., Cambridge, MA, U.S.A. 1996;661-671
6 Wozney JM, Rosen V, Celeste AJ: Novel regulators of bone formation: Molecular clones and activities. Science 1988;242:1528-1534   DOI   PUBMED
7 Yates KE, Troulis MJ, Kaban LB, Glowacki J: IGF-I, TGF-b and BMP-4 are expressed during distraction osteogenesis of the pig mandible. Int J Oral Maxillofac Surg 2002;31:173-178   DOI   ScienceOn
8 Bostrom MP, Lane JM, Berberian WS: Immunolocalization and expression of BMP-2 and -4 in fracture healing. Orthop Res 1995;13:357-367   DOI   ScienceOn
9 Li G, Bouxsein ML, Luppen C: Bone consolidation is enhanced by rhBMP-2 in a rabbit model of distraction osteogenesis. J Orthop Res 2002;20:779-788   DOI   ScienceOn
10 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 1989a;238:249
11 James H. Beaty MD Editor. Orthopaedic knowledge update, 1999;30-32
12 Harris SE, Bonewald LF, Harris MA: Effects of TGFb on bone nodule formation and expression of BMP-2. osteocalcin, osteopontin, alkaline phosphatase, and type 1 collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts. J Bone Miner Res 1994;9:855-863   DOI   PUBMED   ScienceOn
13 Yu Y, Yang JL, Chapman-Sheath PJ, Walsh WR: TGF-beta, BMPs, and their signal transducing mediators, Smads, in rat fracture healing. J Biomed Mater Res 2002;60:392-397   DOI   ScienceOn
14 Campici P, Hamdy RC, Lauzier D, Amako M, Rauch F, Lessard ML: Expression of BMPs during mandibular distraction osteogenesis. Plast Reconstr Surg 2003;111:201-208   DOI   ScienceOn
15 Finkelman RD, Bell NH, Strong DD, Demers LM, Baylink DJ: Ovariectomy selectively reduces the concentration of TGFb in rat bone: implications for estrogen deficiency-associated bone loss. Proc Natl Acad Sci 1992;89:12190-12193.   DOI   ScienceOn
16 Elimak K. Osteoinduction Proteins. Ann Med 1993;25:395-402   DOI   PUBMED   ScienceOn
17 Einhorn TA, Lee CA: Bone regeneration. J Am Acad Orthop Surg 2001;9:157-165   DOI   PUBMED
18 Li G, Berven S, Simpson H, Triffitt JT: Expression of BMP-4 mRNA during distraction osteogenesis in rabbits. Acta Orthop Scand 1998;69:42-45
19 지유진, 송현철, 김여갑, 김 진, 김창현: 신연 골형성술에 있어서의 분자생물학적 최신지견. 대구외지 2002;28:456-463
20 조태준, 최인호, 정진엽: 신연골 형성술과 골절 치유에서 제2형 및 제4형 골형성 단백 유전자 mRNA의 시간적, 공간적 발현. 대한정형외과학회지 1998;33:595-603
21 Sato M, Ochi T, Nakase T, Hirota S, Kitamura Y, Nomura S et al: Mechanical tension-stress induces expression of 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   DOI   ScienceOn
22 Morone MA, Boden SD, Hair G: Gene expression during autograft lumbar spine fusion and the effect of Bone Morphogenetic Protein 2. Clin Orthop 1998;351:252-265
23 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 1989b;239:263
24 Rauch F, Lauzier D, Croteau S, Travers R, Glorieux FH, Hamdy R: Temporal and Spatial expression of BMP-2,-4 and -7 during distraction osteogenesis in rabbits. Bone 2000;27:453-459   DOI   ScienceOn