Browse > Article
http://dx.doi.org/10.14402/jkamprs.2014.36.2.37

Bone Healing in Ovariectomized-rabbit Calvarial Defect with Tricalcium Phosphate Coated with Recombinant Human Bone Morphogenetic Protein-2 Genetically Engineered in Escherichia coli  

Kim, Jung-Han (Department of Oral and Maxillofacial Surgery, Pusan National University School of Dentistry)
Kim, Chang-Joo (Department of Oral and Maxillofacial Surgery, Pusan National University School of Dentistry)
Shin, Sang-Hun (Department of Oral and Maxillofacial Surgery, Pusan National University School of Dentistry)
Publication Information
Maxillofacial Plastic and Reconstructive Surgery / v.36, no.2, 2014 , pp. 37-49 More about this Journal
Abstract
Purpose: This study compares the bone formation ability of tricalcium phosphate (TCP) with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) and assesses TCP as a carrier of rhBMP-2. Methods: Bilateral round defects (diameter: 8.0 mm) were formed in the cranium of eight New Zealand white rabbits. The defects were grafted with TCP only (control group) or with rhBMP-2-coated TCP (experimental group). The animals were sacrificed at 1st week, 2nd week, 4th week, and 8th week postoperatively; two rabbits sacrificed each time. The skulls were harvested and subjected to radiographic and histological examination. Results: Radiologic evaluation showed faster bone remodeling in the experimental group than in the control group. Histologic evaluation (H&E, Masson's trichrome stain) showed rapid bone formation, remodeling and calcification in the 1st and 2nd week in the experimental group. Immunohistochemical evaluation showed higher expression rate of osteoprotegerin, receptor activator of nuclear factor ${\kappa}B$ ligand, and receptor activator of nuclear factor ${\kappa}B$ in the experimental group at the 1st and 2nd week than in the control group. Conclusion: rhBMP-2 coated TCP resulted in rapid bone formation, remodeling, and calcification due to rhBMP-2's osteogenic effect. TCP performed properly as a carrier for rhBMP-2. Thus, the use of an rhBMP-2 coating on TCP had a synergic effect on bone healing and, especially, bone remodeling and maturation.
Keywords
Recombinant human bone morphogenetic protein-2; Tricalcium phosphate; Bone regeneration;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Yang X, Fang J, Luo Y. Effects of recombinant human bone morphogenetic protein 2 and osteogenic agents on proliferation and differentiation of rat mesenchymal stem cells. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2007;21:140-4.
2 Lundgren S, Rosenquist JB. Short term bone healing in calcium deficiency osteopenia and disuse osteopenia: experimental studies in adult rats. Scand J Dent Res 1992;100:337-9.
3 Cao T, Shirota T, Yamazaki M, Ohno K, Michi KI. Bone mineral density in mandibles of ovariectomized rabbits. Clin Oral Implants Res 2001;12:604-8.   DOI
4 Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 2004;15:49-60.   DOI   ScienceOn
5 Theoleyre S, Wittrant Y, Tat SK, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 2004;15:457-75.   DOI   ScienceOn
6 Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42.   DOI   ScienceOn
7 Koide M, Murase Y, Yamato K, Noguchi T, Okahashi N, Nishihara T. Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1alpha through upregulation of osteoclast differentiation factor and cyclooxygenase-2. Biochem Biophys Res Commun 1999;259:97-102.   DOI
8 Kuboki Y, Saito T, Murata M, et al. Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification, respectively; geometrical factors of matrices for celldifferentiation. Connect Tissue Res 1995;32:219-26.   DOI
9 Hughes FJ, Collyer J, Stanfield M, Goodman SA. The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro. Endocrinology 1995;136:2671-7.
10 Higuchi T, Kinoshita A, Takahashi K, Oda S, Ishikawa I. Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling. J Periodontol 1999;70:1026-31.   DOI
11 Matin K, Senpuku H, Hanada N, Ozawa H, Ejiri S. Bone regeneration by recombinant human bone morphogenetic protein-2 around immediate implants: a pilot study in rats. Int J Oral Maxillofac Implants 2003;18:211-7.
12 Ripamonti U, Ma S, Reddi AH. The critical role of geometry of porous hydroxyapatite delivery system in induction of bone by osteogenin, a bone morphogenetic protein. Matrix 1992;12:202-12.   DOI   ScienceOn
13 Urist MR, Lietze A, Dawson E. Beta-tricalcium phosphate delivery system for bone morphogenetic protein. Clin Orthop Relat Res 1984;(187):277-80.
14 Viljanen VV, Gao TJ, Lindholm TC, Lindholm TS, Kommonen B. Xenogeneic moose (Alces alces) bone morphogenetic protein (mBMP)-induced repair of critical-size skull defects in sheep. Int J Oral Maxillofac Surg 1996;25:217-22.   DOI   ScienceOn
15 Kenley R, Marden L, Turek T, Jin L, Ron E, Hollinger JO. Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2). J Biomed Mater Res 1994;28:1139-47.   DOI
16 Misch CE, Dietsh F. Bone-grafting materials in implant dentistry. Implant Dent 1993;2:158-67.   DOI   ScienceOn
17 Pang EK, Im SU, Kim CS, et al. Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model. J Periodontol 2004;75:1364-70.   DOI   ScienceOn
18 Damien CJ, Parsons JR. Bone graft and bone graft substitutes: a review of current technology and applications. J Appl Biomater 1991;2:187-208.   DOI   ScienceOn
19 Ogose A, Kondo N, Umezu H, et al. Histological assessment in grafts of highly purified beta-tricalcium phosphate (OSferion) in human bones. Biomaterials 2006;27:1542-9.   DOI
20 Hollinger JO, Brekke J, Gruskin E, Lee D. Role of bone substitutes. Clin Orthop Relat Res 1996;(324):55-65.
21 Ohgushi H, Okumura M, Tamai S, Shors EC, Caplan AI. Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparative histomorphometric study of ectopic bone formation. J Biomed Mater Res 1990;24:1563-70.   DOI
22 St John KR, Zardiackas LD, Terry RC, Teasdall RD, Cooke SE, Mitias HM. Histological and electron microscopic analysis of tissue response to synthetic composite bone graft in the canine. J Appl Biomater 1995;6:89-97.   DOI
23 Asahina I, Sampath TK, Hauschka PV. Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp Cell Res 1996;222:38-47.   DOI   ScienceOn
24 Knaus P, Sebald W. Cooperativity of binding epitopes and receptor chains in the BMP/TGFbeta superfamily. Biol Chem 2001;382:1189-95.
25 Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22:233-41.   DOI   ScienceOn
26 Okubo Y, Bessho K, Fujimura K, et al. Osteoinduction by recombinant human bone morphogenetic protein-2 at intramuscular, intermuscular, subcutaneous and intrafatty sites. Int J Oral Maxillofac Surg 2000;29:62-6.   DOI   ScienceOn
27 Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988;242:1528-34.   DOI
28 Kirker-Head CA. Potential applications and delivery strategies for bone morphogenetic proteins. Adv Drug Deliv Rev 2000;43:65-92.   DOI   ScienceOn
29 Murata M, Inoue M, Arisue M, Kuboki Y, Nagai N. Carrierdependency of cellular differentiation induced by bone morphogenetic protein in ectopic sites. Int J Oral Maxillofac Surg 1998;27:391-6.   DOI   ScienceOn
30 Nagai N, Qin CL, Nagatsuka H, Inoue M, Ishiwari Y. Age effects on ectopic bone formation induced by purified bone morphogenetic protein. Int J Oral Maxillofac Surg 1999;28:143-50.
31 Kamakura S, Sasano Y, Homma H, Suzuki O, Kagayama M, Motegi K. Implantation of octacalcium phosphate nucleates isolated bone formation in rat skull defects. Oral Dis 2001;7:259-65.   DOI
32 Boyne PJ, Marx RE, Nevins M, et al. A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation. Int J Periodontic Restor Dent 1997;17:11-25.
33 Ohgushi H, Goldberg VM, Caplan AI. Heterotopic osteogenesis in porous ceramics induced by marrow cells. J Orthop Res 1989;7:568-78.   DOI   ScienceOn
34 Bassett CA, Herrmann I. Influence of oxygen concentration and mechanical factors on differentiation of connective tissues in vitro. Nature 1961;190:460-1.   DOI
35 Goldberg VM, Stevenson S. Natural history of autografts and allografts. Clin Orthop Relat Res 1987;(225):7-16.
36 Urist MR. Bone: formation by autoinduction. Science 1965;150:893-9.   DOI   ScienceOn
37 Yasko AW, Lane JM, Fellinger EJ, Rosen V, Wozney JM, Wang EA. The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. J Bone Joint Surg Am 1992;74:659-70.