Role of MAP kinase on MMP-13 expression in rat periodontal ligament cells

백서 치주인대세포에서의 MMP-13 mRNA에 대한 MAP kinase의 역할

  • Chung, Chan-Gil (Department of Periodontology School of Dentistry, Chonnam National University) ;
  • Cui, De-Zhe (Dental Science Research Institute, Chonnam National University) ;
  • Chung, Hyun-Ju (Department of Periodontology School of Dentistry, Dental Science Research Institute, Chonnam National University) ;
  • Kim, Young-Joon (Department of Periodontology School of Dentistry, Dental Science Research Institute, Chonnam National University)
  • 정찬길 (전남대학교 치의학전문대학원 치주과학교실) ;
  • 최득철 (전남대학교 치의학전문대학원 치의학연구소) ;
  • 정현주 (전남대학교 치의학전문대학원 치주과학교실 및 치의학연구소) ;
  • 김영준 (전남대학교 치의학전문대학원 치주과학교실 및 치의학연구소)
  • Published : 2006.03.30

Abstract

Matrix metalloproteinases (MMPs)는 치주조직내에 존재하는 세포외기질의 유지와 분해에 중요한 역할을 담당하고 있으며 이중 MMP-13은 치주질환의 진행과 깊은 관계가 있다고 알려져 있다. 이번 연구는 치주질환의 진행에 있어서 MMP-13의 활성에 대한 mitogen activated protein(MAP) Kinase의 역할을 구명하기 위해 시행되었다. 백서 치주인대세포에서의 MMP-13 mRNA의 발현은 RT-PCR에 의하여, 그리고 MAP Kinase의 발현은 Western blot에 의하여 측정하였다. $Interleukin-1{\beta}$(IL $-1{\beta}$), Tumor necrosis $factora(TNF-{\alpha})$와 parathyroid hormon(PTH)는 MMP- 13 mRNA 발현을 각각 320%, 180%, 380% 증가시켰으나 bone morphogenetic protein-7(BMP-7)은 MMP-13 mRNA의 발현을 증가시키지 않았다. p38 MAP Kinase 억제제인 SB203580은 IL $-1{\beta}$ 유도 MMP-13의 발현을 약 40% 정도 억제시켰으나, PTH-유도 MMP-13 mRNA의 발현은 억제하지 못했다. IL $-1{\beta}$는 MMP- 13 mRNA의 반감기를 약 2시간 정도로 증가시켰으나, p38 MAP Kinase 억제제로 전처치한 경우에는 반감기가 60분으로 줄어들었다. $IL-1{\beta}$는 p38 MAP kinase와 JNK의 인산화 활성을 증가시켰으나 PTH, $TNF-{\alpha}$와 BMP-7은 p38, JNK, ERK의 활성을 증가시키지 못했다. 이상의 연구결과는 p38 MAP Kinase가 백서 치주인대세포에서의 MMP-13 mRNA 발현을 조절하는데 중요한 역할을 담당함을 시사하였다.

Keywords

References

  1. Page RC. and Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab. Invest 1976;34:235-249
  2. Dennison DK. and Van Dyke TE. The acute inflammatory response and the role of phagocytic cells in periodontal health and disease. Periodontol. 2000;14:54-78 https://doi.org/10.1111/j.1600-0757.1997.tb00192.x
  3. Chang Y-C, Yang S-F, Lai C-C, Liu J-Y, Hsieh YS. Regulation of matrix metalloproteinase production by cytokines, pharmacological agents and periodontal pathogens in human periodontal ligament fibroblast cultures. J. Periodont. Res. 2002 ;37:96-203
  4. Domeij H, Yucel-Lindberg T, Moder T. Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival fibroblasts. Eur J Oral Sci. 2002;110: 302-306 https://doi.org/10.1034/j.1600-0722.2002.21247.x
  5. Freije J M P, Diez-Itza I, Balbin M et al. Molecular cloning and expression of collagenase-3. a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem. 1994;269:16766-16773
  6. Tervahartiala T, Pirila E, Ceponis A et al. The in vivo expression of the collagenolytic matrix metalloproteinases (MMP-2, -8, -13, and -14) and matrilysin (MMP-7) in adult and localized juvenile periodontitis. J Dent Res. 2000;79:1969 -1977 https://doi.org/10.1177/00220345000790120801
  7. Ma J, Kitti U, Teronen O, Sorsa T et al. Collagenases in different categories of peri-implant vertical bone loss. J Dent Res. 2000;79:1870-1873 https://doi.org/10.1177/00220345000790110901
  8. Nishikawa M, Yamaguchi Y, Yoshitake K, Saeki Y. Effects of TNFalpha and prostaglandin E2 on the expression of MMPs in human periodontal ligament fibroblasts. J Periodontal Res. 2002;37:167-76 https://doi.org/10.1034/j.1600-0765.2002.00656.x
  9. Gonzalez G.A. and Montminy M.R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989;59:675-680 https://doi.org/10.1016/0092-8674(89)90013-5
  10. Haskill S et al. Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Cell 1991;65:1281-1289 https://doi.org/10.1016/0092-8674(91)90022-Q
  11. Han Z, Boyle DL, Chang L et al. c-Jun N-terminal kinase is required for metal-loproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest. 2001;108:73-81 https://doi.org/10.1172/JCI12466
  12. Patil C, Zhu X, Rossa C Jr, Kim YJ, Kirkwood KL. p38 MAPK regulates IL-1beta induced IL-6 expression through mRNA stability in osteoblasts. Immunol Invest. 2004;33:213-233 https://doi.org/10.1081/IMM-120034231
  13. Seger R. and Krebs EG. The MAPK signaling cascade. FASEB 1995;9:726-735 https://doi.org/10.1096/fasebj.9.9.7601337
  14. Lee HS, Miau LH, Chen CH et al. Differential role of p38 in IL-1alpha induction of MMP-9 and MMP-13 in an established liver myofibroblast cell line. J Biomed Sci. 2003;10:757-765
  15. Ejeil AL, Gaultier F, Igondjo-Tchen S et al. Are cytokines linked to collagen breakdown during periodontal disease progression? J Periodontol 2003;74:196-201 https://doi.org/10.1902/jop.2003.74.2.196
  16. Matsuda N, Kumar M, Ramakrishnan PR et al. 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
  17. Dayer J.M. and H. Fenner. The role of cytokines and their inhibitors in arthritis. Baillieres Clin Rheumatol. 1992;6:485-516 https://doi.org/10.1016/S0950-3579(05)80186-4
  18. Horwood N.J et al. Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 1998;139:4743-6 https://doi.org/10.1210/en.139.11.4743
  19. Lekic P. and McCulloch CA. Periodontal ligament cell population: the central role of fibroblasts in creating a unique tissue. Anat Rec. 1996;245:327-341 https://doi.org/10.1002/(SICI)1097-0185(199606)245:2<327::AID-AR15>3.0.CO;2-R
  20. Kirkwood K, Martin T, Agnello K, Kim YJ. Differential regulation of MMP-13 by chemical modified tetracyclines in osteoblasts. J Int Acad Periodontol. 2004;6:39-46
  21. Shlopov BV, Stuart JM, Gumanovskaya ML, Hasty KA. Regulation of cartilage collagenase by doxycycline. J Rheumatol. 2001;28:835-42
  22. Canalis E, Eydziel S, Delany A, Varghese S, Jeffrey J. Insulin-like growth factors inhibit interstitial collagenase synthesis in bone cell cultures. Endocrinology 1995;136: 1348-1354 https://doi.org/10.1210/en.136.4.1348
  23. Gazzerro E, Rydziel S, Canalis E. Skeletal bone morphogenetic proteins suppress the expression of collagenase-3 by rat osteoblasts. Endocrinology. 1999;140:562-567 https://doi.org/10.1210/en.140.2.562
  24. Mengshol JA, Vincenti MP, Brinckerhoff CE. IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res. 2001;29:4361-4372 https://doi.org/10.1093/nar/29.21.4361
  25. Johansson N, Ala-aho R, Ditto V et al. Expression of collagenass-3 (MMP-13) and collagenase-l (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase. J Cell Sci. 2000;113:227-235
  26. Pillinger MH, Rosenthal PB, Tolani SN et al. Cyclooxygenase-2-derived E prostaglandins down-regulate matrix metalloproteinase-l expression in fibroblast-like synoviocytes via inhibition of extracellular signal-regulated kinase activation. J Immunol. 2003;171:6080-6089 https://doi.org/10.4049/jimmunol.171.11.6080