Osteogenic activity of an adenovirus expressing BMP-2 on Human Periodontal Ligament cells

Adenovirus에 의해서 발현된 BMP-2가 치주인대세포의 분화에 미치는 영향

  • Kim, Kyoung-Hwa (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Park, Yoon-Jeong (Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University) ;
  • Lee, Sang-Cheul (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Kim, Tae-Il (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Seol, Yang-Jo (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Lee, Yong-Moo (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Ku, Young (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Han, Soo-Boo (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Chung, Chong-Pyoung (Department of Periodontology, School of Dentistry, Seoul National University) ;
  • Rhyu, In-Chul (Department of Periodontology, School of Dentistry, Seoul National University)
  • 김경화 (서울대학교 치과대학 치주과학교실) ;
  • 박윤정 (서울대학교 치과대학 두개악안면 재건과학) ;
  • 이상철 (서울대학교 치과대학 치주과학교실) ;
  • 김태일 (서울대학교 치과대학 치주과학교실) ;
  • 설양조 (서울대학교 치과대학 치주과학교실) ;
  • 이용무 (서울대학교 치과대학 치주과학교실) ;
  • 구영 (서울대학교 치과대학 치주과학교실) ;
  • 한수부 (서울대학교 치과대학 치주과학교실) ;
  • 정종평 (서울대학교 치과대학 치주과학교실) ;
  • 류인철 (서울대학교 치과대학 치주과학교실)
  • Published : 2005.06.30

Abstract

The regeneration of lost periodontal tissue is a major goal of therapy. Periodontal ligament cell(PDL) is a specialized connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. Bone morphogenetic proteins(BMPs) have shown much potential in the reconstruction of the periodontum by stimulate new bone and new cementum formation. Limitiations of BMP administration to periodontal lesions is high dose delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene delivery method can be alternative treatment strategy to deliver BMPs to periodontal tissue. The purpose of this study is to investigate efficiency of BMP-2 gene delivery with cell-based therapy using PDL cells. PDL cell were transduced with adenoviruses encoding either BMP-2 or Lac-Z gene. To evaluate osteogenic activity of expressed BMP-2 on PDL cells, we investigated secreted BMP-2, cellular activity, ALPase, produced mineralized nodules. To evaluate collagen scaffold as carrier for transduced cell delivery, we examined morphology and secreted BMP-2 of transducd PDL cells on it. BMP-2 transducd PDL cells produced higher levels of BMP-2, ALPase, mineralized nodules than non transduced cells. Cellular activity of transduced cells was showed similar activity to non transduced cells. Transduce cells attached on collagen scaffold secreted BMP-2 at 7day and was showed similar morphology to non transduced cells. These results demonstrated that transduced PDL cells produced biologically active BMP-2 and collagen scaffold could be carrier of transducd cells.

Keywords

References

  1. Moskow BS. Karsh F. Stein SD. Histological assessment of autogenous bone graft. Acase report and critical evaluation. J Periodontol. 1979 Jun:50(6):291-300 https://doi.org/10.1902/jop.1979.50.6.291
  2. Bulstra s Experiences in human delayed non-unions using OP-1 (BMP-7). Proceedings. First European Conference on Bone Morphogenic Proteins. Abstract 62
  3. Carraro JJ. Sznaider N. Alonso CA. Intraoral cancellous bone autografts in the treatment of infrabony pockets. J Clin Periodontol. 1976 May:3(2):104-9 https://doi.org/10.1111/j.1600-051X.1976.tb01856.x
  4. Garraway R. Young WG. Daley T, Harbrow D, Bartold PM. An assessment of the osteoinductive potential of commercial demineralized freeze-dried bone in the murine thigh muscle implantation model. J Periodontol. 1998 Dec:69(12): 1325-36 https://doi.org/10.1902/jop.1998.69.12.1325
  5. Zybutz MD, Laurell L. Rapoport DA, Persson GR. Treatment of intrabony defects with resorbable materials, nonresorbable materials and flap debridement. J Clin Periodontol. 2000 Mar: 27 (3) : 169-78 https://doi.org/10.1034/j.1600-051x.2000.027003169.x
  6. Takata T.Oral wound healing concepts in periodontology. Curr Opin Periodontol. 1994:119-27
  7. Becker W, Becker BE. Treatment of mandibular 3-wall intrabony defects by flap debridement and expanded polytetrafluoroethylene barrier membranes. Longterm evaluation of 32 treated patients. J Periodontol. 1993:64:1138-44 https://doi.org/10.1902/jop.1993.64.11s.1138
  8. Warrer K, Caton JG, Reid T. A prospective multicenter study evaluating periodontal regeneration for Class II furcation invasions and intrabony defects after treatment with a bioabsorbable barrier membrane: 1-year results. J Periodontol. 1996:67:641-9 https://doi.org/10.1902/jop.1996.67.7.641
  9. Becker W, Lynch SE, Lekholm U et al. A comparison of ePTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freeze-dried bone in promoting bone formation around immediate extraction socket implants. J Periodontol. 1992:63:929-40 https://doi.org/10.1902/jop.1992.63.11.929
  10. Eickholz P, Kim TS, Steinbrenner H et al., Tissue regeneration with bioabsorbable barriers:intrabonv defects and class II furcations. J Periodontol. 2000: 71:999-1008 https://doi.org/10.1902/jop.2000.71.6.999
  11. Oates TW, Rouse CA, Cochran DL., Mitogenic effects of growth factors on human periodontal ligament cells in vitro. J Periodontol. 1993 Feb:64(2):142-8 https://doi.org/10.1902/jop.1993.64.2.142
  12. Piche JE, Graves DT. Study of the growth factor requirements of human bone derived cells: a comparison with human fibroblasts. Bone. 1989:10(2):131-8 https://doi.org/10.1016/8756-3282(89)90011-2
  13. Dennison DK, Vallone DR. Pinero GJ, Rittman B. Caffesse RG. Differential effect of TGF-beta 1 and PDGF on proliferation of periodontal ligament cells and gingival fibroblasts. J Periodontol. 1994 Jul:65(7):641-8 https://doi.org/10.1902/jop.1994.65.7.641
  14. Wozney JM. The potential role of bone morphogenetic proteins in periodontal reconstruction. J Periodontol. 1995:66:506-10 https://doi.org/10.1902/jop.1995.66.6.506
  15. Cochran DL, Wozney JM. Biological mediators for periodontal regeneration. Periodontol 2000. 1999;19:40-58 https://doi.org/10.1111/j.1600-0757.1999.tb00146.x
  16. 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;76:1460-70 https://doi.org/10.1177/00220345970760080801
  17. Kuboki Y, Sasaki M, Saito A, Takita H, Kato H. Regeneration of periodontal ligament and cementum by BMP-applied tissue engineering. Eur J Oral Sci.1998: 106:197-203
  18. Ripamonti U, Reddi AH. Tissue engineering, morphogenesis. and regeneration of the periodontal tissues by bone morphogenetic proteins. Crit Rev Oral Biol Med. 1997:8:154-63 https://doi.org/10.1177/10454411970080020401
  19. 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 https://doi.org/10.1902/jop.1999.70.9.1026
  20. Kobayashi M, Takiguchi T, Suzuki R, et al., Recombinant human bone morphogenetic protein-? stimulates osteoblastic differentiation in cells isolated from human periodontal ligament. J Dent Res. 1999:78:1624-33 https://doi.org/10.1177/00220345990780100701
  21. Sigurdsson TJ. Lee MB. Kubota K et al.. Periodontal repair in dogs: recombinant human bone morphogenetic protein-? significantly enhances periodontal regeneration. J Periodontol. 1995:66:131-8 https://doi.org/10.1902/jop.1995.66.2.131
  22. Barboza EP. Duarte Sorensen RG. Riedel GE, Ridge augmentation following implantation of recombinant human morphogenetic protein-2 in Periodontol. 2000:71:488-96 https://doi.org/10.1902/jop.2000.71.3.488
  23. Howell TH, Fiorellini J, Jones A et al., A feasibility study evaluating rhBMP-2/ absorbable collagen sponge device for local alveolar ridgepreservation or augmentation. Int J Periodontics Restorative Dent. 1997:17:124-39
  24. Terheyden H, Jepsen S, Moller B, Tucker MM, Rueger DC. Sinus floor augmentation with simultaneous placement of dental implants using a combination of deproteinized bone xenografts and recombinant human osteogenic protein-I. A histometric study in miniature pigs. Clin Oral Implants Res. 1999;10:510-21. https://doi.org/10.1034/j.1600-0501.1999.100609.x
  25. Winn SR, Hu Y. Sfeir C. Hollinger JO. Gene therapy approaches for modulating bone regeneration. Adv Drug Deliv Rev. 2000 Aug 20:42(1-2):121-38 https://doi.org/10.1016/S0169-409X(00)00057-0
  26. Crombleholme TM. Adenoviral-mediated gene transfer in wound healing. Wound Repair Regen. 2000 Nov-Dec:8(6):460-72 https://doi.org/10.1046/j.1524-475x.2000.00460.x
  27. Franceschi RT. Wang D. Krebsbach PH, Rutherford RB. Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. J Cell Biochem. 2000 Jun 6:78(3):476-86 https://doi.org/10.1002/1097-4644(20000901)78:3<476::AID-JCB12>3.0.CO;2-5
  28. Baum BJ. Kok M. Tran SD. Yamano S. The impact of gene therapy on dentistry: a revisiting after six years. J Am Dent Assoc. 2002 Jan: 133 (1) : 35-44
  29. Anusaksathien O. Giannobile WV. Growth factor delivery to re-engineer periodontal tissues. Curr Pharm Biotechnol. 2002 Jun:3(2):129-39 https://doi.org/10.2174/1389201023378391
  30. Lieberman JR, Daluiski A, Stevenson S et al.. The effect of regional gene therapy with bone morphogenetic protein- 2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am. 1999 Jul:81(7):905-17
  31. Krebsbach PH, Gu K, Franceschi RT. Rutheford RB. Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo. Hum Gene Ther. 2000 May 20;11(8):1201-10 https://doi.org/10.1089/10430340050015248
  32. Baltzer AW, Lattermann C. Whalen JD et al., Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene. Gene Ther. 2000 May:7(9):734-9
  33. Bartold PM. McCulloch CA, Narayanan AS, Pitaru S. Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000. 2000 Oct:24:253-69 https://doi.org/10.1034/j.1600-0757.2000.2240113.x
  34. Pitaru S, Pritzki A. Bar-Kana I et al., Bone morphogenetic protein 2 induces the expression of cementum attachment protein in human periodontal ligament clones. Connect Tissue Res. 2002:43(2-3):257-64 https://doi.org/10.1080/713713494
  35. Shimono M. Ishikawa T, Ishikawa H et al., Regulatory mechanisms of periodontal regeneration. Microsc Res Tech. 2003 Apr 1:60(5):491-502 https://doi.org/10.1002/jemt.10290
  36. Lekic P, Rojas J, Birek C, Tenenbaum H. McCulloch CA. Phenotypic comparison of periodontal ligament cells in vivo and in vitro. J Periodontal Res. 2001 Apr; 36(2): 71-9 https://doi.org/10.1034/j.1600-0765.2001.360202.x
  37. Ouyang H, McCauley LK. Berry JE et al., Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Arch Oral Biol. 2000 Apr:45(4) :293-303 https://doi.org/10.1016/S0003-9969(99)00142-9
  38. Ohno S, Doi T, Fujimoto K et al., RGDCAP (betaig-h3) exerts a negative regulatory function on mineralization in the human periodontal ligament. J Dent Res. 2002:81(12):822-5 https://doi.org/10.1177/154405910208101205
  39. Han X. Amar S. IGF-1 signaling enhances cell survival in periodontal ligament fibroblasts vs. gingival fibroblasts. J Dent Res. 2003 Jun:82(6) :454-9 https://doi.org/10.1177/154405910308200610
  40. Marcopoulou CE, Vavouraki HN, Dereka XE, Vrotsos IA. Proliferative effect of growth factors TGF-betal, PDGF-BB and rhB:MP-2 on human gingival fibroblasts and periodontal ligament cells. J Int Acad Periodontol. 2003 Jul:5(3):63-70
  41. Zhao M. Berry JE. Somerman MJ. Bone morphogenetic protein-? inhibits differentiation and mineralization of cementoblasts in vitro. J Dent Res. 2003 Jan:82 (1):23-7 https://doi.org/10.1177/154405910308200106
  42. Seo BM. Miura M. Gronthos S et al., Investigation of multipotent postnatal stem cells from human periodontal ligament
  43. Hogan BL.Bone morphogenetic proteins in development. Curr Opin Genet Dev. 1996 Aug:6(4):432-8 https://doi.org/10.1016/S0959-437X(96)80064-5
  44. Reddi AH. Regulation of cartilage and bone differentiation by bone morphogenetic proteins. Curr Opin Cell Biol. 1992 Oct:4(5):850-5 https://doi.org/10.1016/0955-0674(92)90110-X
  45. Kingsley DM. What do BMPs do in mammals? Clues from the mouse short- ear mutation. Trends Genet. 1994 Jan: 10(1):16-21 https://doi.org/10.1016/0168-9525(94)90014-0
  46. Duprez DM. Coltey M. Amthor H, Brickell PM, Tickle C. Bone morphogenetic protein-2 (BMP-2) inhibits muscle development and promotes cartilage formation in chick limb bud cultures. Dev Biol. 1996 Mar 15:174(2):448-52 https://doi.org/10.1006/dbio.1996.0087
  47. Kawasaki K, Aihara M. Honmo J et al.. Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin. Bone. 1998 Sep:23(3):223-31 https://doi.org/10.1016/S8756-3282(98)00105-7
  48. Takiguchi T, Kobayashi M, Suzuki R 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 Periodontal Res. 1998 Nov:33(8):476-85 https://doi.org/10.1111/j.1600-0765.1998.tb02347.x
  49. Cheifetz S. Li IW, McCulloch CA, Sampath K. Sodek J. Influence of osteogenic protein-1 (OP-1; BMP-7) and transforming growth factor-beta 1 on bone formation in vitro. Connect Tissue Res. 1996;35(1-4):71-78 https://doi.org/10.3109/03008209609029176
  50. Ye X. Rivera VM, Zoltick P. Cerasoli F Jr. et al., Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer. Science. 1999 Jan 1: 283 (5398) : 88-91 https://doi.org/10.1126/science.283.5398.88
  51. Krebsbach PH, Gu K. Franceschi RT. Rutherford RB. Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo. Hum Gene Ther. 2000 May 20:11(8):1201-10 https://doi.org/10.1089/10430340050015248