Participation of endogenous IGF-I and TGF-β1 with enamel matrix derivative-stimulated cell growth in human periodontal ligament cells
K. Okubo
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorM. Kobayashi
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorT. Takiguchi
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorT. Takada
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorA. Ohazama
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorY. Okamatsu
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorK. Hasegawa
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorK. Okubo
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorM. Kobayashi
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorT. Takiguchi
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorT. Takada
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorA. Ohazama
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorY. Okamatsu
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorK. Hasegawa
Department of Periodontology, Showa University Dental School, Tokyo, Japan
Search for more papers by this authorAbstract
Previous studies have provided the biological basis for the therapeutic use of enamel matrix derivative (EMD) at sites of periodontal regeneration. A purpose of this study is to determine effects of EMD on cell growth, osteoblastic differentiation and insulin-like growth factor-I (IGF-I) and transforming growth factor-β1 (TGF-β1) production in human periodontal ligament cells (HPLC). We also examined participation of endogenous IGF-I and TGF-β1 with EMD-stimulated cell growth in these cells. HPLCs used in this study were treated with EMD alone or in combination with antihuman IGF-I antibody (anti-hIGF-I) or anti-hTGF-β1, recombinant human bone morphogenetic protein-2 (rhBMP-2), 1,25-dihydroxyvitamin D3[1,25(OH)2D3], rhTGF-β1 or rhIGF-I. After each treatment, cell growth, the production of IGF-I and TGF-β1 and the expression of osteoblastic phenotypes were evaluated. EMD stimulated cell growth in dose-dependent and time-dependent manners. EMD was also stimulated to express IGF-I and TGF-β1 at protein and mRNA levels. The EMD-stimulated cell growth was partially suppressed by cotreatment with anti-hIGF-I or anti-hTGF-β1, and cell growth was also stimulated by treatment with rhIGF-I or rhTGF-β1. rhBMP-2 stimulated alkaline phosphatase (ALPase) activity and ALPase mRNA expression, and 1,25(OH)2D3 stimulated ALPase and osteocalcin mRNA expression. However, EMD showed no effect on the osteoblastic phenotypes expression. These results demonstrated that EMD has no appreciable effect on osteoblastic differentiation, however it stimulates cell growth and IGF-I and TGF-β1 production in HPLC, and that these endogenous growth factors partially relate to the EMD-stimulated cell growth in HPLC.
References
- 1 Gottlow J. Principles of regenerative therapy. In: R Genco, S Hamada, T Lehner, J McGhee, S Mergenhagen, eds. Molecular pathogenesis of periodontal disease. Washington, DC: ASM Press, 1994 : 393–401.
- 2 Cho MI, Matsuda N, Ramakrishnan PR, et al. Differential regulation of periodontal ligament cell activities by platelet-derived growth factor, insulin-like growth factor-I, and epidermal growth factor. In: R Genco, S Hamada, T Lehner, J McGhee, S Mergenhagen, eds. Molecular pathogenesis of periodontal disease. Washington, DC: ASM Press, 1994 : 403–414.
- 3 Cochran DL, Wozney JM. Biological mediators for periodontal regeneration. Periodontol 2000, 1999; 19: 40–58.
- 4 Matsuda N, Lin WL, Kumar NM, Cho MI, Genco RJ. Mitogenic, chemotactic, and synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro. J Periodontol 1992; 63: 515–525.
- 5 Oates TW, Rouse CA, Cochran DL. Mitogenic effects of growth factors on human periodontal ligament cells in vitro. J Periodontol 1993; 64: 142–148.
- 6 Lynch SE, Williams RC, Polson AM, Howell TH, Reddy MS et al. A combination of platelet-derived growth factor and insulin-like growth factor enhances periodontal regeneration. J Clin Periodontol 1989; 16: 545–548.
- 7 Nishimura F, Terranova VP. Comparative study of the chemotactic responses of periodontal ligament cells and gingival fibroblast to polypeptide growth factors. J Dent Res 1996; 75: 986–992.
- 8
Terranova VP,
Wikesjö UME.
Extracellular matrices and polypeptide growth factors as mediators of functions of cells of the periodontium.
J Periodontol
1987; 6: 371–380.
10.1902/jop.1987.58.6.371 Google Scholar
- 9 Blom S, Holmstrup P, Dabelsteen E. The effect of insulin-like growth factor-I and human growth hormone on periodontal ligament fibroblast. J Periodontol 1992; 63: 960–968.
- 10 Takayama S, Murakami S, Miki Y, Ikezawa K, Tasaka S et al. Effects of basic fibroblast growth factor on human periodontal ligament cells. J Periodont Res 1997; 32: 667–675.
- 11 Terranova VP, Odziemiec C, Tweden KS, Spadone DP. Repopulation of dentin surfaces by periodontal ligament cells and endothelial cells. Effect of basic fibroblast growth factor. J Periodontol 1989; 60: 293–301.
- 12 Dennison DK, Vallone DR, Pinero GJ, Rittman B et al. Differential effect of TGF-β1 and PDGF on proliferation of periodontal ligament cells and gingival fibroblast. J Periodontol 1994; 65: 641–648.
- 13 Brady TA, Piesco NP, Buckley MJ, Langkamp HH, Bowen LL et al. Autoregulation of periodontal ligament cell phenotype and functions by transforming growth factor-β1. J Dent Res 1998; 77: 1779–1790.
- 14 Kobayashi M, Takiguchi T, Suzuki R, Yamaguchi A, Deguchi K et al. Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament. J Dent Res 1997; 78: 1624–1633.
- 15 Giannobile WV, Finkelman RD, Lynch SE. Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I. J Periodontol 1994; 65: 1158–1168.
- 16 Lynch SE, Ruiz de Castilla G, Williams RC, Kiritsy CP, Howell TH et al. The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. J Periodontol 1991; 62: 458–467.
- 17 Rutherford RB, Niekrash CE, Kennedy JE, Charette MF. Platelet-derived and insulin-like growth factors stimulate regeneration of periodontal attachment in monkeys. J Periodont Res 1992; 27: 285–290.
- 18 Howell TH, Fiorellini JP, Paquette DW, Offenbacher S, Giannobile WV et al. A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease. J Periodontol 1997; 68: 1186–1193.
- 19 Giannobile WV, Hernandez RA, Finkelman RD, Ryan S, Kiritsy CP et al. Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individually and combination, on periodontal regeneration in Macaca fascicularis. J Periodont Res 1996; 31: 301–312.
- 20 Selvig KA, Wikesjö UME, Bogle GC, Finkelman RD. Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor (II). Basic fibroblast growth factor and transforming growth factor β1. J Clin Periodontol 1994; 21: 380–385.
- 21 Wikesjö UME, Razi SS, Sigurdsson TJ, Tatakis DN, Lee MB et al. Periodontal repair in dogs: effect of recombinant human transforming growth factor-β1 on guided tissue regeneration. J Clin Periodontol 1998; 25: 475–481.
- 22 Ishikawa I, Kinoshita A, Oda S, Roongruanphol T. Regenerative therapy in periodontal diseases. Histological observations after implantation of rhBMP-2 in the surgically created periodontal defects in adult dogs. Dent Jpn 1994; 31: 141–146.
- 23 King GN, King N, Cruchley AT, Wozney JM, Hughes FJ. Recombinant human bone morphogenetic protein-2 promotes wound healing in rat periodontal fenestration defects. J Dent Res 1997; 76: 1460–1470.
- 24 Kinoshita A, Oda S, Takahashi K, Yokota S, Ishikawa I. Periodontal regeneration by application of recombinant human bone morphogenetic protein-2 to horizontal circumferential defects created by experimental periodontitis in beagle dogs. J Periodontol 1997; 68: 103–109.
- 25 Sigurdsson TJ, Lee MB, Kubota K, Turek TJ, Wozney JM et al. Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. J Periodontol 1995; 66: 131–138.
- 26 Sigurdsson TJ, Tatakis DN, Lee MB, Wikesjö UME. Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenetic proteins. J Periodontol 1995; 66: 511–521.
- 27 Brooks SJ, Robinson C, Kirkham J, Bonass WA. Biochemistry and molecular biology of amelogenin proteins of developing dental enamel. Arch Oral Biol 1995; 40: 1–14.
- 28 Hammarström L. Enamel matrix, cementum development and regeneration. J Clin Periodontol 1997; 24: 658–668.
- 29 Hammarström L, Heiji L, Gestrelius S. Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins. J Clin Periodontol 1997; 24: 669–677.
- 30 Heiji L, Heden G, Svärdström G, Östgren A. Enamel matrix derivative (EMDOGAIN®) in the treatment of intrabony periodontal defects. J Clin Periodontol 1997; 24: 705–714.
- 31 Heiji L. Periodontal regeneration with enamel matrix derivative in one human experimental defect. A case report. J Clin Periodontol 1997; 24: 693–696.
- 32 Mellonig JT. Enamel matrix derivative for periodontal reconstructive surgery: technique and clinical and histologic case report. Int J Periodontics Restorative Dent 1999; 19: 9–19.
- 33 Gestrelius S, Andersson C, Lidström D, Hammarström L, Somerman MJ. In vitro studies on periodontal ligament cells and enamel matrix derivative. J Clin Periodontol 1997; 24: 685–692.
- 34 Van Der Pauw MT, Van Den Bos T, Everts V, Beersten W. Enamel matrix-derived protein stimulates attachment of periodontal ligament fibroblasts and enhances alkaline phosphatase activity and transforming growth factor β1 release of periodontal ligament and gingival fibroblasts. J Periodontol 2000; 71: 31–43.
- 35 Hoang AM, Oates TW, Cochran DL. In vitro wound healing responses to enamel matrix derivative. J Periodontol 2000; 71: 1270–1277.
- 36 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.
- 37 Hou LT, Liu CM, Lei JY, Wong MY, Chen JK. Biological effects of cementum and bone extracts on human periodontal fibroblasts. J Periodontol 2000; 71: 1100–1109.
- 38 Takiguchi T, Kobayashi M, Suzuki R, Yamaguchi A, Isatsu K et al. Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae. J Periodont Res 1998; 33: 476–485.