만성 치주염 환자에서 2형 당뇨병이 $PGE_2$, MMP-14 및 TIMP의 발현양상에 미치는 영향

The Influence of Diabetes on of $PGE_2$, MMP-14 and TIMP Expressions in Human Chronic Periodontitis

  • 김선우 (경북대학교 치과대학 치주과학교실) ;
  • 박진우 (경북대학교 치과대학 치주과학교실) ;
  • 서조영 (경북대학교 치과대학 치주과학교실) ;
  • 이재목 (경북대학교 치과대학 치주과학교실)
  • Kim, Seon-Woo (Department of Periodontology, School of Dentistry, Kyungpook National University) ;
  • Park, Jin-Woo (Department of Periodontology, School of Dentistry, Kyungpook National University) ;
  • Suh, Jo-Young (Department of Periodontology, School of Dentistry, Kyungpook National University) ;
  • Lee, Jae-Mok (Department of Periodontology, School of Dentistry, Kyungpook National University)
  • 발행 : 2007.12.31

초록

Purpose: The purposes of this study were to compare and quantify the expression of $PGE_2$, MMP-14 and TIMP-1 in the gingival tissues of patients with type 2 diabetes mellitus and healthy adults of chronic periodontitis with alveolar bone resorption. Material and methods: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1 (n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2 (n=8) is inflammed gingiva from patients of chronic periodontitis with alveolar bone resorption. Group 3(n=8) is inflammed gingiva from patients of chronic periodontitis with alveolar bone resorption associated with type 2 diabetes. Tissue samples were prepared and analyzed by Western blotting. The quantification of $PGE_2$ MMP-14 and TIMP-1 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. Results: The expressions of MMP-14 and TIMP-1 were showed increasing tendency in group 2 & 3 compared to group 1. The expressions of $PGE_2$, MMP-14 were showed increasing tendency in group 3 compared to group 1 and group 2. According to MMP-14 levels were increasing, $PGE_2$ showed increasing tendency in group 3, and although $PGE_2$, MMP-14 levels were increasing, TIMP-1 levels were similar expressed comparing to group 2. Conclusion: In conclusion, this study demonstrated that the expression levels of MMP-14 and TIMP-1 had increasing tendency in inflammed tissue. It can be assumed that $PGE_2$ and MMP-14 may be partly involved in alveolar bone resorptive process and the progression of periodontal inflammation associated to type 2 DM.

키워드

참고문헌

  1. Emrich LJ, Shlosman M and Genco RJ. Periodontal disease in non-insulin dependent diabetes mellitus. J Periodontol 1991; 62:123-129 https://doi.org/10.1902/jop.1991.62.2.123
  2. Taylor GW, Burt BA, Becker MP et al. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. J Periodontol 1998;69:76-83 https://doi.org/10.1902/jop.1998.69.1.76
  3. Collin H-L, Uusitupa M and Niskanen L. Periodontal findings in elderly patient with non-insulin depedent diabetes mellitus. J Periodontol 1998;69:962-966 https://doi.org/10.1902/jop.1998.69.9.962
  4. Salvi GE, Yalda B, Collins JG. Inflammatory Mediator Response as a Potential Risk Marker for Periodontal Diseases in Insulin-Dependent Diabetes mellitus patients. J Periodontol 1997;68:127-135 https://doi.org/10.1902/jop.1997.68.2.127
  5. AAP Position Paper. Diabetes and peridontal disease. J Periodontol 1999;70:935-949 https://doi.org/10.1902/jop.1999.70.8.935
  6. Bissada NF, Manoucher-Pour M, Haddow M and Spagnulo PJ. Neutrophil functional activity in juvenile and adult onset diabetic patients with mild and severe periodontitis. J Periodont Res 1982;17:500-502 https://doi.org/10.1111/j.1600-0765.1982.tb02038.x
  7. Page RC and Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest 1976;34:235-249
  8. Zhong Y, Slade GD, Beck JD, Offenbacher S. Gingival crevicular fluid interleukin-1beta, prostaglandin E2 and periodontal status in a community population. J Clin Periodontol 2007;34(4) :285-93 https://doi.org/10.1111/j.1600-051X.2007.01057.x
  9. Offenbacher S, Heasman PA, Collins JG. Modulation of host $PGE_2$ secretion as a determinant of periodontal disease expression. J Periodontol 1993;64:432-444
  10. Matejka M, Ulm C, Nell A et al. Stimulation of PGI2 synthesis in the periodontal tissue by interleukin -1$\alpha$ and -1$\beta$ Adv Exp Med Biol 1997;433:443-446
  11. Noguchi K, Shitashige M, Ishikawa I. Involvement of cyclooxygenase-2 in interleukin la -induced prostaglandin production by human periodontal ligament cells. J Periodontol 1999;70:902-908 https://doi.org/10.1902/jop.1999.70.8.902
  12. O'Neill GP, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 1993;330:156-160
  13. Ryan EM and Golub LM. Modulation of Matrix metalloproteinase activities in periodontitis as a treatment strategy. Periodontology 2000 2000;24:226-238 https://doi.org/10.1034/j.1600-0757.2000.2240111.x
  14. Birkendal-Hansen H. Role of Matrix Metalloproteinases In Human Periodontal Diseases. J Periodontol 1993;64:474-484
  15. Chang Y-C, Yang S-F, Lai C-C, Liu J-Y and Hsieh Y-S. Regulation of matrix metalloproteinase production by cytokines, pharmacological agents and periodontal pathogens in human periodontal ligament fibroblast cultures. J Periodont Res 2002; 37:196-203 https://doi.org/10.1034/j.1600-0765.2002.00663.x
  16. Uitto VJ, Overall CM and McCulloch C. Proteolytic host cell enzymes in gingival crevice fluid. Periodentology 2000 2003;31: 77-104 https://doi.org/10.1034/j.1600-0757.2003.03106.x
  17. H. Sato, T. Takino, Y. Okada et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells, Nature 1994;370:61-65 https://doi.org/10.1038/370061a0
  18. M. Seiki. The cell surface: the stage for matrix metalloproteinase regulation of migration' Curr. Opin. Cell Biol. 2002;14:624-632 https://doi.org/10.1016/S0955-0674(02)00363-0
  19. R. Achong, I Nishimura, H. Ramachandran et al. Membrane Type(MT)1-matrix metalloproteinase( MMP) and MMP-2 expression in ligature-induced periodontitis in the rat. J Periodontol 2003;74:494-500 https://doi.org/10.1902/jop.2003.74.4.494
  20. Erwin van der Zee, Everts V and Beertsen W. Cytokines modulate routes of collagen breakdown. J Clin Periodontol 1997;24:297-305 https://doi.org/10.1111/j.1600-051X.1997.tb00761.x
  21. Kang MG, Cha HG, Song SH et al. MMP-2, MMP-8 Expression in gingival tissue of chronic periodontitis associated to Type 2 Diabetes Mellitus. Journal of Korean Academy of Periodontology 2005;35:661-674
  22. Cho JY, Xing S, Liu X et al. Expression and activity of human Na+/I- symporter in human glioma cells by adenovirus-mediated gene delivary. Gene Therapy 2000;7:740-749
  23. Offenbacher S, Odle BM, Van Dyke TE. The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. J Periodont Res 1986;21:101-112 https://doi.org/10.1111/j.1600-0765.1986.tb01443.x
  24. Birkedal-Hansen H. Role of cytokines and inflammatory mediators in tissue destruction. J Periodont Res 1993;28:500-510 https://doi.org/10.1111/j.1600-0765.1993.tb02113.x
  25. Mundy, GR. Inflammatory mediators and the destruction of bone. J Periodont Res 1991;26:213-217 https://doi.org/10.1111/j.1600-0765.1991.tb01647.x
  26. Socransky SS, Haffajee AD, Goodson JM, Lindhe J. New concepts of destructive periodontal disease. J Clin Periodontol 1984;11:21-32 https://doi.org/10.1111/j.1600-051X.1984.tb01305.x
  27. Golub LM, Lee HM, Lehrer G. Minocycline reduces gingivalcollagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. J Periodont Res 1983;18:516-526 https://doi.org/10.1111/j.1600-0765.1983.tb00388.x
  28. Trengove NJ. Stacey MC. MacAuley S et al. Analysis of the acute and chronic wound environments: the role of proteases and the inhibitors. Wound Repair Regeneration 1999;7:442-52 https://doi.org/10.1046/j.1524-475X.1999.00442.x
  29. Ohuchi E, Imai K, Fujii Y et al. Membrane type-1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 1997;272:24413-2451
  30. Kuauper V, Will H, Lopez-Otin C et al. Cellular mechanisms, for human procollagenase-3 (MMP-13) activation. Evidence that MTI-MMP (MMP-14) and gelatinase A(MMP-2) are able to generate active enzyme. J Biol Chem 1996;271:17124-17131 https://doi.org/10.1074/jbc.271.29.17124
  31. Drouin L, Overall CM, Sodea J. Identification of matrix metalloproteinase inhibitor (TIMP) in human parotid saliva : partial purification and characterization. J Periodont Res 1988;23:370-377 https://doi.org/10.1111/j.1600-0765.1988.tb01615.x
  32. Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem 1999;274: 21491-21494 https://doi.org/10.1074/jbc.274.31.21491
  33. Hayakawa H, Yamashita K, Ohwaki K. Collagenase activity and tissue inhibitor of metalloproteinases-1(TIMP-1)content in human whole saliva from clinically healthy and periodontally diseased subjects, J Periodont Res 1994;29:305-308 https://doi.org/10.1111/j.1600-0765.1994.tb01226.x
  34. Ryan ME, Ramamurthy NS, Sorsa T, Golub LM. MMP-mediated events in diabetes. Ann NY Acad Sci 1999;873:311-314
  35. Choi DH, Moon IS, Choi BK et al. Effects of sub-antimic robial dose doxycycline therapy on crevicular fluid MMP-8 and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitis. J Periodont Res 2004;39:20-26 https://doi.org/10.1111/j.1600-0765.2004.00696.x