Journal of Periodontal and Implant Science

  • 제36권2호
  • /
  • Pages.335-344
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  • 2006
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  • 2093-2278(pISSN)
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  • 2093-2286(eISSN)
대한치주과학회 (Korean Academy of Periodontology)
권호 표지

백서 치주인대세포에서 Doxycycline에 의한 mRANKL 발현 억제

Inhibition of mRANKL Expression by Doxycycline in Rat Periodontal Ligament Cells

  • 조관표 (전남대학교 치의학전문대학원 치주과학교실) ;
  • 최득철 (전남대학교 치의학전문대학원 치의학연구소) ;
  • 김영준 (전남대학교 치의학전문대학원 치주과학교실, 치의학연구소)
  • Cho, Kwan-Pyo (Department of Periodontology, Chonnam National University) ;
  • Cui, De-Zhe (Dental Science Research Institute, Chonnam National University) ;
  • Kim, Young-Joon (Department of Periodontology, Dental Science Research Institute, Chonnam National University)
  • 발행 : 2006.06.30
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초록

Osteoblast or bone marrow stromal cell-derived RANKL is the major effector molecule essential for osteoclastogenesis. Previous studies have shown that tetracyclines have beneficial therapeutic effects in the prevention and treatment of inflammatory bone disease including periodontal disease. Periodontal ligament cells are thought not only to play an important role in the progression of periodontal disease, but to play an important role in alveolar bone remodeling. Previous studies indicated that receptor activation of nuclear factor $\kappa\;B$ ligand (RANKL) and osteoprotegerin (OPG) are expressed in periodontal ligament cells by pro-inflammatory cytokine, such as $IL-1{\beta}$ and $TNF-{\alpha}$. This study was designed to investigate the inhibitory effect of doxycycline on RANKL and OPG mRNA in rat periodontal ligament cells induced by $IL-1{\beta}$ (1 ng/ml). The results are as follows; 1. MTT assay showed that doxycycline at the concentration of $1-50\;{\mu}g/m{\ell}$ didn't result in statistically significant cell death at day 1 and 3. 2. RANKL mRNA expression was increased to 2.6 folds by $IL-1{\beta}$. When cells were treated with doxycycline ($50{\mu}g/m{\ell}$), $IL-1{\beta}$ -induced mRANKL expression was reduced by 33%. In contrast to RANKL, OPG mRNA expression was not inhibited by pre-treatment with doxycycline. These results suggest that doxycycline decrease the expression of mRANKL resulting in regulation of osteoclastogenesisp in rat periodontal ligament cells.

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참고문헌

  1. Pitaru S, McCulloch CAG, Narayanan SA.. Cellular origins and differentiation control mechanical during periodontal development and wound healing. J Periodont Res 1994 2;9:81-94
  2. Mundy GR. Role of cytokines in bone resorption. J Cell Biochem 1993;53:296-300 https://doi.org/10.1002/jcb.240530405
  3. Kumar S, Votta BJ, Riemann DJ, Badger AM, Gowen M, Lee JC. IL-1 and NF-induced bone resorption is mediated by p38 mitogen activated protein kinase. J Cell Physiol 2001;187:294-303 https://doi.org/10.1002/jcp.1082
  4. Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H, Sakai H. Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kB ligand; modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Comm 2000;275:768-775 https://doi.org/10.1006/bbrc.2000.3379
  5. Hofbauer LC and Heufelder AE. Role of receptor activator of nuclear factor-kB ligand and osteoprotegerin in bone cell biology. J Mol Med 2001:79:243-253 https://doi.org/10.1007/s001090100226
  6. Siggelkow H. Eidner T. Lehmann G. Viereck V. Raddatz D. Munzel U. Hein G. Hufner M. Cytokines, osteoprotegerin, and RANKL in vitro and histomorphometric indices of bone turnover in patients with different bone diseases. J Bone Miner Res 2003;18:529-538 https://doi.org/10.1359/jbmr.2003.18.3.529
  7. Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, Inoue J. Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J 2001;20:1271-1280 https://doi.org/10.1093/emboj/20.6.1271
  8. Rani CS and MacDougall M. Dental cells express factors that regulate bone resorption. Mol Cell Biol Res Comm 2000;3:145-152 https://doi.org/10.1006/mcbr.2000.0205
  9. Kanzaki H. Chiba M. Shimizu Y. Mitani H. Dual regulation of osteoclast differentiation by periodontal ligament cells through RANKL stimulation and OPG inhibition. J Dent Res 2001;80:887-891 https://doi.org/10.1177/00220345010800030801
  10. 김종철, 김영준, 정혅주, 김옥수. 백서 치주인대 세포의 RANKL 발현에 대한 p38 MAPK의 역할. 대한치주과학회지 2004;34:489-498
  11. Slots J, Mashimo P, Levine MJ, Genco RJ. Periodontal theray in humans. I. Microbilogical and clinical effects of a single course of periodontal scaling and root planing, and of adjunctive tetracycline therapy. J Periodontol 1979;50:495-509 https://doi.org/10.1902/jop.1979.50.10.495
  12. Walker CB, Gordon JM, McQuilken SJ, Niebloom TA. Levels achievable in gingival crevice fluid and in vitro effect on subgingival organism. Part III. Susceptibilities of periodontal bacteria. J Periodontol 1981;52:613-616 https://doi.org/10.1902/jop.1981.52.10.613
  13. Lindhe J, Liljenberg B, Adielsson B. Effect of long-term tetracycline therapy of human periodontal disease. J Clin Periodontol 1983;10:590-601 https://doi.org/10.1111/j.1600-051X.1983.tb01297.x
  14. Golub L, Ramamurthy N, McNamara TF, Gomes B, Wolff M, Casino A, Kapoor A, Zambon J, Ciancio S, Schneir M, Perry H. Tetracyclines inhibit tissue collagenase activity: A new mechanism in the treatment of periodontal disease. J Periodont Res 1984;19:651-655 https://doi.org/10.1111/j.1600-0765.1984.tb01334.x
  15. Seymour RA and Heacman PA. Tetracyclines in the management of periodontal diseases. J Clin Periodontol 1995;22:22-35 https://doi.org/10.1111/j.1600-051X.1995.tb01767.x
  16. Kirkwood KL, Golub LM, Bradford PG. Non-antimicrobial and antimicrobial tetracyclines inhibit IL-6 expression in murine osteoblasts. Ann N Y Acad Sci 1999;878:667-670 https://doi.org/10.1111/j.1749-6632.1999.tb07757.x
  17. Kirkwood K, Martin T, Andreadis ST, Kim YJ. Chemically modified tetracyclines selectively inhibit IL-6 expression in osteoblasts by decreasing mRNA stability. Biochem Pharmacol 2003;66:1809-1819 https://doi.org/10.1016/S0006-2952(03)00450-7
  18. Ramamurthy NS, Rifkin BR, Greenwald RA, Xu JW, Liu Y, Turner G, Golub LM, Vernillo AT. Inhibition of matrix metalloproteinase-mediated periodontal bone loss in rats: a comparison of 6 chemically modified tetracyclines. J Periodontol 2002;73:726-734 https://doi.org/10.1902/jop.2002.73.7.726
  19. E-Attar TM, Lin HS, Shultz R. Effect of minocycline on prostaglandin formation in gingival fibroblasts. J Periodontal Res 1988;23:285-286 https://doi.org/10.1111/j.1600-0765.1988.tb01418.x
  20. Matsuda N, Kumar M, Ramakrishnan PR, Lin WL, Genco RJ, Cho MI. Evidence for up-regulation of epidermal growth factors on rat periodontal ligament fibroblastic cells associated with stabilization of phenotype in vitro. Arch Oral Biol 1993;38:559-569 https://doi.org/10.1016/0003-9969(93)90120-B
  21. Genco RJ, Goldman HM, Cohen DW. Contemporary periodontics. CV Mosdy, St Louis, 47-54, 1990
  22. Pascale D, Gordon J, Lamster I, Mann P, Seiger M, Arndt W. Concentration of doxycycline in human gingival fluid. J Clin Periodontol 1986;13:841-847 https://doi.org/10.1111/j.1600-051X.1986.tb02240.x
  23. Golub LM, Sorsa T, Lee HM, Ciancio S, Sorbi D, Ramamurthy NS, Gruber B, Salo T, Konttinen YT. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J Clin Periodontol 1995;22: 100-109 https://doi.org/10.1111/j.1600-051X.1995.tb00120.x
  24. Zhao N, Yang PS, Ge SH, Qi XM, Sun QF. Biological effects of tetracycline and doxycycline on cultured human periodontal ligament cells. Shanghai Kou Qiang Yi Xue. 2003;12(4):269-272
  25. Tsukuda N and Gabler WL. The influence of doxycycline of the attachment of fibroblasts to gelatin-coated surfaces and its cytotoxicity. J Periodontol 1993;64:1219-1224 https://doi.org/10.1902/jop.1993.64.12.1219
  26. Gordon JM, Walker CB, Murphy JC, Socransky SS. Concentration of tetracycline in human gingival fluid after single doses. J Clin Periodontol 1981;8:117-121 https://doi.org/10.1111/j.1600-051X.1981.tb02351.x
  27. 조종휘, 김상목, 김병옥, 한경윤. 테트라사이클린게 약물이 치은섬유아세포내 MMP-3의 활성도에 미치는 영향. 대한치주과학회지 1999;29:677-691
  28. Li DQ, Lokeshwar BL, Solomon A, Monroy D, Ji Z, Pflugfelder SC. Regulation of MMP-9 production by human corneal epithelial cells. Exp Eye Res 2001;73:449-459 https://doi.org/10.1006/exer.2001.1054
  29. Shlopov BV, Stuart JM, Gumanovskaya ML, Hasty KA. Regulation of cartilage collagenase by doxycycline. J Rheumatol 2001;28:835-842
  30. Kirkwood KL, Ziegler L, Sigurdson W. Expression profiling of gene regulated by chemically modified tetracycline-8 in murine osteoblastic cells. J Dent Res 2001; 80:120
  31. Kirkwood K, Martin T, Andreadis ST, Kim YJ. Chemically modified tetracyclines selectively inhibit IL-6 expression in osteoblasts by decreasing mRNA stability. Biochem Pharmacol. 2003;66:1809-1819 https://doi.org/10.1016/S0006-2952(03)00450-7