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Journal of Dental Research
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Recombinant Human Bone Morphogenetic Protein-2 Promotes Wound Healing in Rat Periodontal Fenestration Defects

G.N. King

Department of Periodontology

N. King

Department of Periodontology

A.T. Cruchley

Department of Oral Pathology, Faculty of Clinical Dentistry, St Bartholomew's & The Royal London School of Medicine & Dentistry, Turner St., London El AD, United Kingdom

J.M. Wozney

Genetics Institute, Cambridge, Massachusetts, USA

F.J. Hughes

Department of Periodontology

Although there is considerable interest in the use of bone morphogenetic protein (BMP) to promote periodontal regeneration, little is known of its effects on the early stages of wound healing. The aim of this study was to investigate the effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an early stage of post-operative wound healing and following complete healing (10 and 38 days, respectively) in a rat model of periodontal regeneration. The buccal aspects of molar roots were carefully denuded of their periodontal ligament through a bony window created in the mandibles of Wistar rats under general anesthesia. After the root surfaces were acid-conditioned, a 10-µL quantity of 50 µg/mL rhBMP-2 in a collagen gel solution was placed into the surgically created defect in test animals; in controls, either a 10-µL quantity of only collagen gel was received, or the defect was untreated. Animals were killed 10 days or 38 days after surgery and the tissues processed for histological examination. Transverse 5-um sections were stained for the identification of new bone, cementum, and collagen fiber formation. In the 10-day study groups, new bone formation over the second molar and beyond the defect was significantly increased in the test group (p < 0.02), although there was no evidence of increased ankylosis. RhBMP-2 stimulated more than twice the area of cementum growth coronally compared with controls (712 ± 286 µm2 and 258 ± 57 µm2, respectively). Connective tissue attachment, including the number and width of collagen bundles, was similar in both test and controls. Complete healing without any evidence of ankylosis had occurred in all animals 38 days postoperatively, and no significant differences were observed between test and control groups. In conclusion, a single dose of rhBMP-2 increased the rate of normal intramembranous bone formation and selectively enhanced cementum formation coronally during early wound healing. However, the finding that rhBMP-2 induced bone formation at some distance from the defect suggests the importance of developing a suitable delivery system to maintain the concentration of BMP-2 at the site of implantation for potential therapeutic use.

Key Words: growth factors • periodontal regeneration • bone morphogenetic protein • wound healing.

REFERENCES

  • Asahina I., Sampath TK, Nishimura I., Hauschka PV (1993). Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 123:921-933.[Abstract/Free Full Text]
  • Beertsen W., Everts V. (1990). Formation of acellular root cementum in relation to dental and non-dental hard tissues in the rat. J Dent Res 69:1669-1673.
  • Blomlof J., Jansson L., Blomlof L., Lindskog S. (1995). Long-time etching at low pH jeopardizes periodontal healing. J Clin Periodontol 22:459-463.[CrossRef][Medline] [Order article via Infotrieve]
  • Blomlof J., Jansson L., Blomlof L., Lindskog S. (1996). Root surface etching at neutral pH promotes periodontal healing. J Clin Periodontol 23:50-55.[Medline] [Order article via Infotrieve]
  • Bradbury P., Gordon KC (1990). Connective tissues and stains. In: Theory and practice of histological techniques. Bancroft JD, Stevens A, editors. Edinburgh: Churchill Livingstone, p. 132.
  • Caton J., Mota L., Landini L., Laskaris B. (1994). Non-human primate models for testing the efficacy and safety of periodontal regeneration procedures. J Periodontol 65:1143-1150.[Medline] [Order article via Infotrieve]
  • Celeste AJ, Iannazzi JA, Taylor RC, Hewick RM, Rosen V., Wang EA, et al. (1990). Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. Proc Natl Acad Sci USA 87:9843-9847.[Abstract/Free Full Text]
  • Chen TL, Bates RL, Dudley A., Hammonds RG Jr, Amento EP (1991). Bone morphogenetic protein-2b stimulation of growth and osteogenic phenotypes in rat osteoblast-like cells: comparison with TGF-beta 1. J Bone Min Res 6:1387-1393.[Medline] [Order article via Infotrieve]
  • Cho MI, Garant PR (1989). Radioautographic study of [3H]-mannose utilization during cementoblast differentiation, formation of cellular cementum and development of periodontal ligament principal fibers. Anat Rec 223:209-222.[CrossRef][Medline] [Order article via Infotrieve]
  • Elsdale T., Bard J. ( 1972). Collagen substrata for studies on cell behavior. J Cell Biol 54 626-637.[Abstract/Free Full Text]
  • Fernyhough W., Page RC ( 1983). Attachment, growth and synthesis by human gingival fibroblasts on demineralized or fibronectin-treated normal and diseased tooth roots. J Periodontol 54:133-140.[Medline] [Order article via Infotrieve]
  • Garrett SJ, Crigger M., Egelberg J. (1978). Effects of citric acid on diseased root surfaces. J Periodontol 13:155-163.
  • Hanes PJ, Polson AM (1989). Cell and fiber attachment to demineralized cementum from normal root surfaces. J Periodontol 60:188-198.[Medline] [Order article via Infotrieve]
  • Hanes PJ, Polson AM, Ladenheim S. (1985). Cell and fiber attachment to demineralized dentin from normal root surfaces. J Periodontol 56:752-765.[Medline] [Order article via Infotrieve]
  • Hughes FJ, Collyer J., Stanfield M., Goodman SA (1995). The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro. Endocrinol 136:2671-2677.[Abstract]
  • Katagiri T., Yamaguchi A., Ikeda T., Yoshiki S., Wozney JM, Rosen V., et al. (1990). The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun 172:295-299.[CrossRef][Medline] [Order article via Infotrieve]
  • Macneil RL, Sheng N., Strayhorn C., Fisher LW, Somerman MJ (1994). Bone sialoprotein is localized to the root surface during cementogenesis. J Bone Min Res 9:1597-1606.[Medline] [Order article via Infotrieve]
  • Melcher AH, Cheong T., Cox J., Nemeth E., Shiga A. (1986). Synthesis of cementum-like tissue in vitro by cells cultured from bone: a light and electron microscopic study. J Periodont Res 21: 592-612.[CrossRef][Medline] [Order article via Infotrieve]
  • Polson AM, Hanes PJ (1987). Cell and fiber attachment to demineralized dentin. A comparison between normal and periodontitis-affected root surfaces. J Clin Periodontol 14:357-365.[Medline] [Order article via Infotrieve]
  • Polson AM, Frederick GT, Ladenheim S., Hanes PJ (1983). The production of a root surface smear layer by instrumentation and its removal by citric acid. J Periodontol 55:443-446.
  • Ripamonti U., Heliotis M., van den Heever B., Reddi AH (1994). Bone morphogenetic proteins induce periodontal regeneration in baboons (Papio ursinus). J Periodont Res 29:439-445.[CrossRef][Medline] [Order article via Infotrieve]
  • Rutherford RB, Ryan ME, Kennedy JE, Tucker MM, Charette MF (1993a). Platelet-derived growth factor and
  • dexamethasone combined with a collagen matrix induce regeneration of the periodontium in monkeys. J Periodontol 20:537-544.
  • Rutherford RB, Wahle J., Tucker M., Rueger D., Charette M. (1993b). Induction of reparative dentin formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol 38:571-576.[CrossRef][Medline] [Order article via Infotrieve]
  • Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H., Tucker RF, et al. (1992). 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 267:20352-20362.[Abstract/Free Full Text]
  • Selvig KA (1994). Discussion: Animal models in reconstructive therapy. J Periodontol 65:1169-1172.[Medline] [Order article via Infotrieve]
  • Selvig KA, Wikesjo Ume, Bogle GC, Finkelman RD (1994). Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor II, basic fibroblast growth factor beta-1. J Clin Periodontol 21:380-385.[Medline] [Order article via Infotrieve]
  • Sigurdsson TJ, Lee MB, Kubota K., Turek TJ, Wozney JM, Wikesjo UM (1995). Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. J Periodontol 66:131-138.[Medline] [Order article via Infotrieve]
  • Tenorio D., Cruchley A., Hughes FJ (1993a). Immunocytochemical investigation of the rat cementoblast phenotype. J Periodont Res 28:411-419.[Medline] [Order article via Infotrieve]
  • Tenorio D., Goodman SA, Hughes FJ (1993b). Bone morphogenetic protein 2 (BMP-2) expression in the developing rat tooth germ (abstract). J Dent Res 72:713.
  • Tenorio D., Cruchley A., Hughes F. (1995). The investigation of the expression of PTH receptors in rat cementoblasts. Arch Oral Biol 41:299-305.
  • Thies RS, Bauduy M., Ashton BA, Kurtzberg L., Wozney JM, Rosen V. (1992). Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. Endocrinol 130:1318-1324.[Abstract/Free Full Text]
  • Urist MR (1965). Bone formation by autoinduction. Science 150:893-899.[Abstract/Free Full Text]
  • Wang EA, Rosen V., D'Alessandro JS, Bauduy M., Cordes P., Harada T., et al. (1990). Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87:2220-2224.[Abstract/Free Full Text]
  • Wang EA, Israel DI, Kelly S., Luxenberg DP (1993). Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. Growth Factors 9:57-71.[Medline] [Order article via Infotrieve]
  • Wesselink PR, Beertsen W. (1994). Repair processes in the periodontium following dentoalveolar ankylosis: the effect of masticatory function. Clin Periodontol 21:472-478.
  • Wetterwald A., Hofstetter W., Cecchini MG, Lanske B., Wagner C., Fleisch H. (1996). Characterization and cloning of the Ell antigen, a marker expressed by rat osteoblasts and osteocytes. Bone 18:125-132.
  • Wozney JM (1993). Bone morphogenetic proteins and their gene expression. In: Cellular and molecular biology of bone. Noda M, editor. San Diego, CA: Academic Press Inc., pp. 131-167.
  • Wozney JM, Rosen V., Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, et al. (1988). Novel regulators of bone formation: molecular clones and activities. Science 242:1528-1534.[Abstract/Free Full Text]
  • Yamaguchi A., Katagiri T., Ikeda T., Wozney JM, Rosen V., Wang EA, et al. (1991). Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J Cell Biol 113: 681-687.[Abstract/Free Full Text]

Journal of Dental Research, Vol. 76, No. 8, 1460-1470 (1997)
DOI: 10.1177/00220345970760080801


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This Article
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