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Journal of Dental Research
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Matrix Metalloproteinases (MMP-2 and MMP-9) of the Oral Cavity: Cellular Origin and Relationship to Periodontal Status

M. Makela

Department of Oral Surgery, University of Oulu, Finland

T. Salo

Department of Oral Surgery, University of Oulu, Finland

V.-J. Uitto

University of British Columbia, Departments of Oral Biology and Clinical Dental Sciences, Vancouver, BC V6T 1Z3, Canada

H. Larjava

University of British Columbia, Departments of Oral Biology and Clinical Dental Sciences, Vancouver, BC V6T 1Z3, Canada

Proteolytic enzymes released by the host cells are associated with the tissue destruction in periodontal diseases. Matrix metalloproteinases (MMPs) have the primary role in this process, since, in concert, they can degrade most of the extracellular matrix components. In the present study, we investigated MMP-2 and MMP-9 in oral fluids of healthy subjects and periodontitis patients and the contributions of different oral cells to the enzyme production. The enzymograms revealed that the main gelatinase in oral rinses, crevicular fluid, and whole saliva migrated at 92 kDa. Activity was also detected at 200 kDa and 130 kDa and minor activity at 86 kDa, 72 kDa, and 40 kDa. Traces of gelatinolytic activity were also detected in pure parotid secretions. The 92-kDa enzyme was identified to MMP-9 and the 200-kDa gelatinase to MMP-2, by means of specific anti-72-kDa antiserum. Gingival keratinocytes produced mainly MMP-9, while gingival and granulation tissue fibroblasts expressed MMP-2. Glandular tissue contained mainly MMP-9, and mRNA for MMP-9 was also found in acinar epithelial cells. Periodontitis patients had significantly higher levels of MMP-9 than healthy subjects. Also, MMP-2 was elevated in periodontitis patients. Periodontal treatment reduced the amount of gelatinases dramatically. This study shows that gelatinases are produced by various cells in the oral cavity. The amount of gelatinases is elevated during periodontal disease, while conventional periodontal treatment efficiently reduces the levels these enzymes. We suggest that MMP-2 and MMP-9 could participate in tissue destruction in periodontitis.

Key Words: Enzymes • Gingival Crevicular Fluid • Periodontal Diseases • Saliva

REFERENCES

  • Autio-Harmainen H., Sandberg M., Pihlajaniemi T., Vuorio E. (1991). Basement membrane synthesis in developing placenta. J Lab Invest 4:483-491.
  • Chen J.-M, Aimes R., Ward GR, Youngleib GL, Quigley AJ (1991). Isolation and characterization of a 70-kDa metalloproteinase (gelatinase) that is elevated in Rous sarcoma virus-transformed chicken embryo fibroblasts. J Biol Chem 266:5113-5121.[Abstract/Free Full Text]
  • Davis GE (1991). Identification of an abundant latent 94-kDa gelatin-degrading metalloproteinase in human saliva which is activated by acid exposure: implications for a role in digestion of collagenous proteins. Arch Biochem Biophys 286:551-554.[CrossRef][Medline] [Order article via Infotrieve]
  • Drouin L., Overall CM, Sodek J. (1988). Identification of matrix metalloendoproteinase inhibitor (TIMP) in human parotid and submandibular saliva: partial purification and characterization. J Periodont Res 23:370-377.[CrossRef][Medline] [Order article via Infotrieve]
  • Fessler LI, Duncan KG, Fessler J., Salo T., Tryggvason K. (1984). Characterization of procollagen IV cleavage products produced by a specific tumor collagenase. J Biol Chem 259:9783-9789.[Abstract/Free Full Text]
  • Gangbar S., Overall CM, McCulloch CAG, Sodek J. (1990). Identification of polymorphonuclear leukocyte collagenase and gelatinase activities in mouthrinse samples: correlation with periodontal disease activity and juvenile periodontitis. J Periodont Res 25:257-267.[CrossRef][Medline] [Order article via Infotrieve]
  • Heussen C., Dowdle EB (1980). Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulphate and copolymerized substrates. J Anal Biochem 102:196-202.[CrossRef][Medline] [Order article via Infotrieve]
  • Hibbs MS, Hasty KA, Kang AH, Mainardi CL (1984). Secretion of collagenolytic enzymes by human polymorphonuclear leukocytes. J Collagen Rel Res 4:467-477.
  • Hibbs MS, Hasty KA, Seyer JM, Kang AH, Mainardi CI (1985). Biochemical and immunological characterization of the secreted forms of human neutrophil gelatinase. J Biol Chem 260:2493-2500.[Abstract/Free Full Text]
  • Hakkinen L., Larjava H. (1992). Characterization of fibroblast clones from periodontal granulation tissue in vitro. J Dent Res 71:1901-1907.
  • Kalebic T., Garbisa S., Glaser B., Liotta LA (1983). Basement membrane collagen: degradation by migrating endothelial cells. Science 221:281-283.[Abstract/Free Full Text]
  • Laemmli UK (1970). Cleavage of structural proteins during the assembly of bacteriophage T4. Nature 227:680-685.[CrossRef][Medline] [Order article via Infotrieve]
  • Mainardi CL, Hibbs MS, Hasty KS, Seyer JM (1984). Purification of a type V collagen degrading enzyme from rabbit alveolar macrophages. Collagen Rel Res 4:479-492.
  • Nieminen A., Nordlund L., Uitto V.-J (1993). The effect of treatment on the activity of salivary proteases and glycosidases in adults with advanced periodontitis. J Periodontol 64:297-301.[Medline] [Order article via Infotrieve]
  • Ogata Y., Enghild JJ, Nagase H. (1992). Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 267:3581-3584.[Abstract/Free Full Text]
  • O'Grady RL, Nethery A., Hunter N. (1984). A fluorescent screening assay for collagenase using collagen labeled with L-methoxy-2,4-diphenyl-3(2H) furanone. Anal Biochem 140:490-494.[CrossRef][Medline] [Order article via Infotrieve]
  • Okada Y., Nakanishi I. (1989). Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 ('gelatinase') by human neutrophil elastase and cathepsin G. FEBS Lett 249:353-356.[CrossRef][Medline] [Order article via Infotrieve]
  • Okada Y., Watanabe S., Nakanishi I., Kishi J., Hayakawa T., Watorek W., et al. (1988). Inactivation of tissue inhibitor of metalloproteinases by neutrophil elastase and other serine proteases. FEBS Lett 229:157-160.[CrossRef][Medline] [Order article via Infotrieve]
  • Okada Y., Mordomi T., Enghild JJ, Suzuki K., Yasui A., Nakanishi I., et al. (1990). Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymatic properties. Eur J Biochem 194:721-730.[Medline] [Order article via Infotrieve]
  • Overall CM, Wrana JL, Sodek J. (1989). Independent regulation of collagenase, 72-kDa progelatinase and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-β. J Biol Chem 264:1860-1869.[Abstract/Free Full Text]
  • Overall CM, Sodek J., McCulloch CAG, Birek P. (1991). Evidence for polymorphonuclear leukocyte collagenase and 92-kilodalton gelatinase in gingival crevicular fluid. Infect Immun 59:4687-4692.[Abstract/Free Full Text]
  • Rifas L., Halstead RL, Peck WA, Avioli LV, Welgus HG (1989). Human osteoblasts in vitro secrete tissue inhibitor of metalloproteinases and gelatinase but not interstitial collagenase as major products. J Clin Invest 84:686-694.[Medline] [Order article via Infotrieve]
  • Risteli L., Risteli J. (1987). Analysis of extracellular matrix proteins in biological fluids. J Meth Enzymol 145:391-411.
  • Salo T., Turpeenniemi-Hujanen T., Tryggvason K. (1985). Tumor-promoting phorbol esters and cell proliferation stimulate secretion of basement-membrane (type IV) collagen degrading metalloproteinase by human fibroblasts. J Biol Chem 260:8526-8531.[Abstract/Free Full Text]
  • Salo T., Lyons JG, Rahemtulla F., Birkedal-Hansen H., Larjava H. (1991). Transforming growth factor beta-I up-regulates type IV collagenase expression in cultured human keratinocytes. J Biol Chem 266:11436-11441.[Abstract/Free Full Text]
  • Salo T., Makela M., Kylmaniemi M., Autio-Harmainen H., Larjava H. (1994). Expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (72 kDa and 92 kDa type IV collagenases) during early human wound healing. Lab Invest 70:176-182.[Medline] [Order article via Infotrieve]
  • Schiott CR, Löe H. (1970). The origin and variation in number of leukocytes in human saliva. J Periodont Res 5:36-41.[Medline] [Order article via Infotrieve]
  • Seltzer JL, Adams SA, Grant GA, Eisen AZ (1981). Purification and properties of a gelatin-specific neutral protease from human skin. J Biol Chem 256:4662-4668.[Abstract/Free Full Text]
  • Seltzer JL, Eisen AZ, Bauer EA, Morris NP, Glanville RW, Burgeson RE (1989). Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (gelatinase) derived from human skin. J Biol Chem 264:3822-3826.[Abstract/Free Full Text]
  • Seltzer JL, Akers KT, Weingarten H., Grant GA, McCourt DW, Eisen AZ (1990). Cleavage specificity of type IV collagenase (gelatinase). J Biol Chem 265:20409-20413.[Abstract/Free Full Text]
  • Senior RM, Griffin GL, Fliszar CJ, Shapiro SD, Goldberg GI, Welgus HG (1991). Human 92- and 72-kilodalton type IV collagenases and elastases. J Biol Chem 266:7870-7875.[Abstract/Free Full Text]
  • Soini Y., Autio-Harmainen H. (1993). Synthesis and degradation of basement membranes in benign and malignant salivary gland tumors. A study by in situ hybridization. J Pathol 170:291-296.[Medline] [Order article via Infotrieve]
  • Sorsa T., Uitto V.-J, Suomalainen K., Vauhkonen M., Lindy S. (1988). Comparison of interstitial collagenases from human gingiva, sulcular fluid and polymorphonuclear leukocytes. J Periodont Res 23:386-393.[CrossRef][Medline] [Order article via Infotrieve]
  • Sorsa T., Ingman T., Suomalainen K., Haapasalo M., Konttinen Y., Lindy O., et al. (1992). Identification of proteases from potent periodontopathogenic bacteria as activators of latent human neutrophil and fibroblast-type interstitial collagenases. Infect Immun 60:4491-4495.[Abstract/Free Full Text]
  • Teng YT, Sodek J., McCulloch CAG (1992). Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. J Periodont Res 27:544-552.[CrossRef][Medline] [Order article via Infotrieve]
  • Uitto V.-J, Suomalainen K., Sorsa T. (1990). Salivary collagenase. Origin, characteristics and relationship to periodontal health. J Periodont Res 25:135-142.[CrossRef][Medline] [Order article via Infotrieve]
  • Unemori EN, Hibbs MS, Amento E. (1991). Constitutive expression of 92-kD gelatinase (type IV collagenase) by rheumatoid synovial fibroblasts and its induction in normal human fibroblasts by inflammatory cytokines. J Clin Invest 88:1656-1662.[Medline] [Order article via Infotrieve]
  • Vartio T., Baumann A. (1989). Human gelatinase/type IV collagenase is a regular plasma component. FEBS Lett 255:285-289.[CrossRef][Medline] [Order article via Infotrieve]
  • Watanabe T., Ohata N., Morishita M., Iwamoto Y. (1981). Correlation between the protease activities and the number of epithelial cells in human saliva. J Dent Res 60:1039-1044.
  • Weiss SJ, Peppin G., Ortiz X., Ragsdale C., Test ST ( 1985). Oxidative autoactivation of latent collagenase by human neutrophils. Science 227:747-749.[Abstract/Free Full Text]
  • Werb Z. ( 1989). Proteinases and matrix degradation. In: Textbook of rheumatology. 3rd ed. Kelly WN, Harris ED Jr, Ruddy S, Sledge CB, editors. Philadelphia: Saunders, pp 300-321.
  • Woodley DT, Kalebic T., Banes RJ, Link W., Pruniers M., Liotta L. (1987). Adult human keratinocytes migrating over nonviable dermal collagen produce collagenolytic enzymes that degrade type I and type IV collagen. J Invest Dermatol 86:418-423.

Journal of Dental Research, Vol. 73, No. 8, 1397-1406 (1994)
DOI: 10.1177/00220345940730080201


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