Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
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The effect of rhBMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization

골형성유도단백질의 첨가가 ${\Delta}^{12}-PGJ_2$가 유도하는 석회화에 미치는 영향

  • Kim, Won-Kyung (Department of Dentistry, Asan Medical Center) ;
  • Kim, Kyoung-Hwa (Department of Periodontology, Seoul National University) ;
  • Kim, Jong-Jin (Department of Dentistry, Asan Medical Center) ;
  • Lee, Young-Kyu (Department of Dentistry, Asan Medical Center) ;
  • Ku, Young (Department of Periodontology, Seoul National University)
  • 김원경 (서울 아산병원 치과) ;
  • 김경화 (서울대학교 치과대학 치주과학교실) ;
  • 김종진 (서울 아산병원 치과) ;
  • 이영규 (서울 아산병원 치과) ;
  • 구영 (서울대학교 치과대학 치주과학교실)
  • Published : 2005.06.30
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Abstract

Prostaglandin plays a significant role in the local control of bone metabolism associated with periodontal disease. ${\Delta}^{12}-PGJ_2$ is a natural $PGD_2$ metabolite that is formed in vivo in the presence of plasma. It is known for ${\Delta}^{12}-PGJ_2$ to stimulate calcification in osteoblastic cells. Bone morphogenetic protein(BMP) stimulated osteoblastic differentiation in various types of cells and greatly enhanced healing of bony defects. The purpose of this study was to evaluate the effect of rhEMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization in vitro. A human osteosarcoma cells line Saos-2 were cultured. In the test groups, 10-7M of ${\Delta}^{12}-PGJ_2$ or mixture of 10-8M of ${\Delta}^{12}-PGJ_2$ and 100ng/ml of rhBMP-2 or 100ng/ml of rhEMP-2 were added to culture media. After 1 day, 2 days and 4 days of culture period, the cell number was measured. Alkaline phosphatase activity was measure at 3 days. Reverse transcription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein at 8 hours, 1 day and 7 days. The ability to produce mineralized nodules in rat osteoblasts(MC3T3-E1) was evaluated at 21 days. The results were as follows : 1. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ inhibited cell proliferation of human osteosarcoma cells. 2. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated alkaline phosphatase activity significantly higher than ${\Delta}^{12}-PGJ_2$ alone. 3. rhBMP-2 or mixture of rhEMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated mineralization compared to ${\Delta}^{12}-PGJ_2$ alone. 4. mRNA of alkaline phosphatase, BMP-2, cbfa 1, Type I collagen were detected in the group treated with ${\Delta}^{12}-PGJ_2$/rhBMP-2, rhBMP-2 alone, ${\Delta}^{12}-PGJ_2$ alone. These results show that mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 causes more bone formation than ${\Delta}^{12}-PGJ_2$ alone while the bone formation effects of mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 are less than those of rhBMP-2 alone. Further researches would be necessary to clarify the interactions of these agents.

Keywords

References

  1. Altiere ET. Reeve CM & Sheridan PJ. Lyophilized bone allografts in periodontal intraosseous defects. J Periodontol 1979;50:510-526 https://doi.org/10.1902/jop.1979.50.10.510
  2. Bowers G, Felton F, Middleton C, et al. Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freezedried bone allograft and with purified bovine collagen. J Periodontol 1991;62:690-702 https://doi.org/10.1902/jop.1991.62.11.690
  3. Caffesse RG, Smith BA, Duff B, et al. Class II fur cations treated by guided tissue regeneration in humans: case reports J Periodontol 1990;61:510-514 https://doi.org/10.1902/jop.1990.61.8.510
  4. Carraro JJ. Sznajder N & Alonso CA, Intraoral cancellous bone autografts in the treatment of infrabony pockets. J Clincal Periodontol 1976;3:104-109 https://doi.org/10.1111/j.1600-051X.1976.tb01856.x
  5. Tomford WW. Current concepts review. Transmission of disease through transplantation of musculoskeletal allografts. J. Bone and Joint Surg, 1995;77-A:1742-1754
  6. Urist MR. DeLange RJ. Finerman GAM. one cell differentiation and growth factors : induced activity of chondro-osteogenic DNA. Science 1983:220:680-686 https://doi.org/10.1126/science.6403986
  7. Asahina I, Sampath TK, Nishimura I, et al. Human osteogenic proteirn-I induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 1993;123:921-933 https://doi.org/10.1083/jcb.123.4.921
  8. Christopher L, Strayhorn J, Stephen Garrett, et al. Gorwth factors regulate expression of osteoblast-associated genes J periodontol 1999;70:1345-1354
  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. Endodont 1995;136:2671-2677
  10. 김현종, 최상묵, 구영 등. 치주인대세포와 치은 섬유아세포의 분화에 미치는 rh BMP-2의 효과에 대한 연구. 대한치주과학회지 2002;32:389-402
  11. Knutsen R, Wergedal JE, Sampath TK, Baylink DJ, Mohan S. Osteogenic protein-1 stimulates proliferation and differentiation of human bone cells in vitro. Biochem Biophys Res Commun. 1993;194:1352-1358 https://doi.org/10.1006/bbrc.1993.1973
  12. King GN, King N, Hughes FJ. Effect of two delivery systems for recombinant human bone morphogenetic protein-2 on periodontal regeneration in vivo. J Periodont Res 1998;33:226-236 https://doi.org/10.1111/j.1600-0765.1998.tb02194.x
  13. Ripamonti U, Heliotis M, Vander Heerer B, Reddi AH. Bone morphogenetic proteins induce periodontal regeneration in the baboon(papioursinus). J Periodont Res 1994;29:439-445 https://doi.org/10.1111/j.1600-0765.1994.tb01246.x
  14. Sigurdsson TJ, Tatakis DN, Lee MB, Wikesjo UME. Periodontal regenerative potential of space-providing expanded polvtetrafluoroethylene membranes and recombinant human bone morphogenetic proteins. J Periodontol 1995;66:511-521 https://doi.org/10.1902/jop.1995.66.6.511
  15. Barbozoa EP, Caula AL, Caula FO, et al. Effect of Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge with spaceproviding biomaterials on the augment a tion of chronic alveolar ridge defects. J Periodontol 2004;75:702-708 https://doi.org/10.1902/jop.2004.75.5.702
  16. Noshi T, Yoshikawa T, Dohi Y, et al. Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic ability of marro/hydroxyapatite composites Artificial Organs 2001;25:201-208 https://doi.org/10.1046/j.1525-1594.2001.025003201.x
  17. Schwartz Z, Weesner T, Van Dijk S, et al. Ability of deproteinized cancellous bovine bone to induce new bone formation. J Periodontol 2000;71:1258-1269 https://doi.org/10.1902/jop.2000.71.8.1258
  18. Sigurdsson TJ, Fu E. Tatakis DN, Rohrer :MD, Wikesjo UME Bone morphogenetic protein-? for peri-implant bone regeneration and osseointegration Clin Oral Impl Res 1997;8:367-374 https://doi.org/10.1034/j.1600-0501.1997.080503.x
  19. Zegzula HD, Buck DC, Brekke J, et al. Bone formation with use of rhBMP-2 J Bone & Joint Surgery 1997;79-A 1778-1790
  20. Cochran DL, Jones AA, Lilly Le, et al. Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants: 3-year results of a pilot study in humans. J Periodontol 2000;71:1241-1257 https://doi.org/10.1902/jop.2000.71.8.1241
  21. Jung RE, Glauser R. Scharer P, et al. Effect of rhBMP-2 on guided bone regeneration in humans. A randomized, controlled clinical and histomorphometric study. Cli. Oral Impl. Res. 2003;14:556-568 https://doi.org/10.1034/j.1600-0501.2003.00921.x
  22. Bilezikian JP, Raisz LG, Rodan GA. Principles of bone biology, 2nd ed. Academic Press, 2002;979-994
  23. Offenbacher S, Collins JG, Heasman PA Diagnostic potential of host response mediators. Advances in Dental Research 1993;7:175-181
  24. Offenbacher S, Odle BM. Gray RC, Van Dyke TE. Crevicular fluid prostaglandin E level as a measure of periodontal disease status of adult and juvenile periodontitis patients. J Periodont Res 1984;19:1-13 https://doi.org/10.1111/j.1600-0765.1984.tb01190.x
  25. Offenbacher S, Heasman PA. Collins JG. Modulation of host PG2 secretion as a determinant of periodontal disease expression, J Periodontol 1993;64:432-444
  26. Klein DC, Raisz LG. Prostaglandins: Stimulation of bone resorption in tissue culture. Endocrinology 1970;86:1436-1440 https://doi.org/10.1210/endo-86-6-1436
  27. Flanagan AM, Chambers TJ. Stimulation of bone nodule formation in vitro by prostaglandins E1 and E2. Endocrinology 1992;130:443-448 https://doi.org/10.1210/en.130.1.443
  28. Jee WS, Ma YF. The in vivo anabolic actions of prostaglandins in bone. Bone 1997;21:297-304 https://doi.org/10.1016/S8756-3282(97)00147-6
  29. Ono I. Inoue M Kuboki Y. Promotion of the osteogenetic activity of recombinant human bone morphogenetic protein by prostaglandin E1. Bone 1996;19:581-588 https://doi.org/10.1016/S8756-3282(96)00282-7
  30. Weinreb M. Suponitzky I. Keila S. Systemic administration of an anabolic dose of PGE2 in youg rats increases the osteogenic capacity of bone marrow. Bone 1997;20:521-526 https://doi.org/10.1016/S8756-3282(97)00033-1
  31. Hakeda Y, Hiramatsu M, Tsunoi M, Kumegawa M. Inductive effects of prostaglandins on alkaline phosphatase in osteoblastic cells, clone MCT3-E1 J Biochem 1985;97:97-104
  32. Fukushima M. Prostaglandin J2-antitumor and anti-viral activities and mechanisms involved. Eicosanoids 1999;3:189-199
  33. Tasaki Y, Takamori R, Koshihara Y. Prostaglandin D2 stimulates collagen synthesis by human osteoblasts during calcification. Prostaglandins 1991;41:303-313 https://doi.org/10.1016/0090-6980(91)90001-V
  34. Koshihara Y, Kawamura M. Prostaglandin D2 stimulates calcification of human osteoblastic cells. Biochem Biophys Res Commun 1989;159:1206-1212 https://doi.org/10.1016/0006-291X(89)92238-9
  35. 허정미, 김경화, 정경욱, 이혜준, 류인철, 구영, 정종평. ${\Delta}^{12}PGJ_2$ 및 PPAR 감마 길항체가 조골세포의 증식 및 분화에 미치는 효과. 대한치주과학회지 2005;35(1):13152
  36. Takagi T, Yamamoto T, Asano S, Tamaki H. Effect of prostaglandin D2 on the femoral bone mineral density in ovariectomized rats. Calcified Tissue 1993;52:442-446 https://doi.org/10.1007/BF00571334
  37. Kobayashi M. Takicuchi T, Suzuki R, et al. Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differenciation in cells isolated from human periodontal ligament. J Dent Res 1999;78:1624-1633 https://doi.org/10.1177/00220345990780100701
  38. Lian J. Stein GS. Concepts of osteoblast growth and differentiation; Basic for modulation of bone cell development and tissue formation. Crit Rev Oral Bio Med 1992;3:269-305
  39. Yao KL. Todescan R. Sod J. Temporal changes in matrix protein synthesis and mRNA expression during mineralized tissue formation by adult rat bone marrow cells in culture. J Bone Miner Res 1994;9:231-240
  40. Lecanda F, Avioli LV, Cheng SL. Regulation of bone matrix protein expression and human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2. J Cell Biochem. 1997;67:386-396 https://doi.org/10.1002/(SICI)1097-4644(19971201)67:3<386::AID-JCB10>3.0.CO;2-B