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
Restricted accessOtherFirst published online December, 2000
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
Periodontal inflammation is characterized by irreversible degradation of periodontal ligament collagen fibers leading to loss of tooth attachment. Cultured gingival keratinocytes and fibroblasts express, in vitro, various matrix metalloproteinases (MMPs) which can degrade fibrillar collagens. We hypothesized that several MMPs are also synthesized in vivo by sulcular epithelium, and analyzed the collagenolytic MMPs (MMP-2, -8, -13, and -14) and matrilysin (MMP-7) in gingival tissue specimens and gingival crevicular fluid from adult and localized juvenile periodontitis patients by in situ hybridization, immunohistochemistry, and Western immunoblotting. MMP-2, -7, -8, and -13 were expressed in gingival sulcular epithelium. MMP-7 and -13 were also located in fibroblasts and macrophages, and MMP-8 in neutrophils. MMP-8- and -13-positive cells/mm2 were higher in periodontitis gingiva when compared with healthy control tissue (p < 0.01). In periodontal diseases, gingival sulcular epithelium expresses several, rather than a single, collagenolytic MMPs, and this proteolytic cascade is evidently responsible for the tissue destruction characteristic of adult and juvenile periodontitis.
Ainamo J., Bay I. (1975). Problems and proposals for recording gingivitis and plaque. Int Dent J25:229-235.
2.
Aimes RT, Quigley JP (1995). Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem270:5872-5876.
3.
Baer PN ( 1971). The case for periodontosis as a clinical entity . J Periodontol42:516-520.
4.
Balbin M., Fueyo A., Knauper V., Pendas AM, Lopez JM, Jiminez MG, et al. (1998). Collagenase 2 (MMP-8) expression in murine tissue remodeling processes. Analysis of its potential role in postpartum involution of the uterus. J Biol Chem273 :23959-23968.
5.
Birkedal-Hansen H. (1993). Role of matrix metalloproteinases in human periodontal diseases. J Periodontol64(5 Suppl) :474-484.
6.
Chen HY, Cox SW, Eley BM, Mantyla P., Ronka H., Sorsa T. (2000). Matrix metalloproteinase-8 levels and elastase activities in gingival crevicular fluid from chronic adult periodontitis patients . J Clin Periodontol27:366-369.
7.
Ciancio S., Ashley R. (1998). Safety and efficacy of subantimicrobial-dose doxycycline therapy in patients with adult periodontitis. Adv Dent Res12:27-31.
8.
Crabbe T., Smith B., O'Connell J., Docherty A. (1994). Human progelatinase A can be activated by matrilysin . FEBS Lett345:14-16.
9.
Ding Y., Uitto V.-J, Firth J., Salo T., Haapasalo M., Konttinen YT, et al. (1995). Modulation of host matrix metalloproteinases by bacterial virulence factors relevant in human periodontal diseases. Oral Dis1:279-286.
10.
Freije JM, Diez-Itza I., Balbin M., Sanchez LM, Blasco R., Tolivia J., et al. (1994). Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem269:16766-16773.
11.
Giambernardi TA, Grant GM, Taylor GP, Hay RJ, Maher VM, McCormick JJ, et al. (1998). Overview of matrix metalloproteinase expression in cultured human cells. Matrix Biol16:483-496.
12.
Golub LM, Sorsa T., Lee HM, Ciancio S., Sorbi D., Ramamurthy NS, et al. (1995). Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J Clin Periodontol22:100-109.
13.
Golub LM, Lee HM, Greenwald RA, Ryan ME, Sorsa T., Salo T., et al. (1997). A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments and specific collagenases in gingival crevicular fluid during adult periodontitis. Inflamm Res46:310-319.
14.
Hanemaaijer R., Sorsa T., Konttinen YT, Ding Y., Sutinen M., Visser H., et al. (1997). Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by TNF-a and doxycycline. J Biol Chem272:31504-31509.
15.
Imai K., Yokohama Y., Nakanishi I., Ohuchi E., Fujii Y., Nakai N., et al. (1995). Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties. J Biol Chem270:6691-6697.
16.
Ingman T., Sorsa T., Michaelis J., Konttinen YT (1994). Immunohistochemical study of neutrophil- and fibroblast-type collagenases and stromelysin-1 in adult periodontitis. Scand J Dent Res102:342-349.
17.
Ingman T., Tervahartiala T., Ding Y., Tschesche H., Haerian A., Kinane DF, et al. (1996). Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients. J Clin Periodontol23:1127-1132.
18.
Johnson RB, Streckfus CF, Dai X., Tucci MA (1999). Protein recovery from several paper types used to collect gingival crevicular fluid. J Periodont Res34:283-289.
19.
Knauper V., Lopez-Otin C., Smith B., Knight G., Murphy G. (1996a). Biochemical characterization of human collagenase-3 . J Biol Chem271:1544-1550.
20.
Knauper V., Will H., Lopez-Otin C., Smith B., Atkinson SJ, Stanton H., et al. (1996b). Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase A (MMP-2) are able to generate active enzyme. JBiol Chem271:17124-17131.
21.
Koivunen E., Arap W., Valtanen H., Rainisalo A., Medina OP, Heikkila P., et al. (1999). Tumor targeting with a selective gelatinase inhibitor. Nat Biotechnol17:768-774.
22.
Konttinen YT, Ceponis A., Takagi M., Ainola M., Sorsa T., Sutinen M., et al. (1998). New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above. Matrix Biol17:585-601.
23.
Konttinen YT, Salo T., Hanemaaijer R., Valleala H., Sorsa T., Sutinen M., et al. (1999). Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate. Matrix Biol18:401-412.
24.
Lee W., Aitken S., Sodek J., McCulloch Cag (1995). Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: role of active enzyme in human periodontitis. J Periodont Res30:23-33.
25.
Li H., Bauzon DE, Xu X., Tschesche H., Cao J., Sang QA ( 1998). Immunological characterization of cell-surface and soluble forms of membrane type 1 matrix metalloproteinase in human breast cancer cells and in fibroblasts. Mol Carcinog22:84-94.
26.
Lindhe J., Nyman S. (1985). Examination of patients with periodontal disease . In: Textbook of clinical periodontology. Lindhe J editor. Copenhagen, Denmark: Munksgaard, pp. 298-308.
27.
Lindy 0, Konttinen YT, Sorsa T., Ding Y., Santavirta S., Ceponis A., et al. (1997). Matrix metalloproteinases 13 (collagenase 3) in human rheumatoid synovium. Arthritis Rheum40:1391-1399.
28.
Llavaneras A., Golub LM, Rifkin BR, Heikkila P., Sorsa T., Teronen 0, et al. (1999). CMT-8/clodronate combination therapy synergistically inhibits alveolar bone loss in LPS-induced periodontitis. Ann NY Acad Sci878:671-674.
29.
Makela M., Larjava H., Pirila E., Maisi P., Salo T., Sorsa T., et al. (1999). Matrix metalloproteinase-2 (gelatinase A) is related to migration of keratinocytes. Exp Cell Res251:67-78.
30.
Mancini S., Romanelli R., Laschinger CA, Overall CM, Sodek J., McCulloch CA (1999). Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases. J Periodontol70:1292-1302.
31.
Nomura T., Ishii A., Oishi Y., Kohma H., Hara K. ( 1998). Tissue inhibitors of metalloproteinases level and collagenase activity in gingival crevicular fluid: the relevance to periodontal diseases . Oral Dis4:231-240.
32.
Ohuchi E., Imai K., Fujii Y., Sato H., Seiki M., Okada Y. (1997). Membrane type-1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem272:2446-2451.
33.
Okada A., Bellocq J-P., Rouyer N., Chenard M-P., Rio M.-C, Chambon P., et al. (1995). Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA92:2730-2734.
34.
Palosaari H., Wahlgren J., Larmas M., Ronka H., Sorsa T., Salo T., et al. (2000). The expression of MMP-8 in odontoblasts and dental pulp cells is down-regulated by TGF-β1. J Dent Res79:77-84.
35.
Pirila E., Ramamurthy N., Maisi P., McClain S., Kucine A., Wahlgren J., et al. (2000). Wound healing in ovariectomized rats. Effects of chemically modified tetracycline (CMT-8) and estrogen on matrix metalloproteinases -8, -13 and type I collagen expression. Curr Med Chem (in press).
36.
Prikk K., Maisi P., Pirila E., Sepper R., Salo T., Wahlgren J., et al. (2000). In vivo expression of collagenase-2 (MMP-8) by human bronchial epithelial cells and monocyte/macrophages in bronchiectasis . J Pathol (in press).
37.
Romanelli R., Mancini S., Laschinger C., Overall CM, Sodek J., McCulloch Cag (1999). Activation of neutrophil collagenase in
38.
periodontitis. Infect Immun67:2319-2326.
39.
Rosin M., Benjamin P., Royers P., Gibson M., Van Leuven F., Johansson NW, et al. (1995). Elevated conversion of alpha-2-macroglobulin to the complexed form in gingival crevicular fluid from adult periodontitis patients. J Periodont Res30:436-444.
40.
Sorsa T., Ding Y., Salo T., Lauhio A., Teronen 0, Ingman T., et al. (1994). Effects of tetracyclines on neutrophil, gingival, and salivary collagenases. A functional and Western blot assessment with special reference to their cellular sources in periodontal diseases. Ann NYAcad Sci732:112-131.
41.
Sorsa T., Mantyla P., Ronka H., Kallio P., Kallis GB, Lundqvist C., et al. (1999). Scientific basis of a matrix metalloproteinase-8 specific chair-side test for monitoring periodontal and peri-implant health and disease. Ann NY Acad Sci878:130-140.
42.
Teronen 0, Heikkila P., Konttinen YT, Laitinen M., Salo T., Hanemaaijer R., et al. (1999). MMP inhibition and downregulation by bisphosphonates . Ann NY Acad Sci878:453-465.
43.
von Bredow DC, Cress AE, Howard EW, Bowden GT, Nagle RB (1998). Activation of gelatinase-tissue-inhibitors-of-metalloproteinase complexes by matrilysin. Biochem J 331 (Pt3):965-972.
44.
Wahlgren J., Maisi P., Sorsa T., Sutinen T., Tervahartiala T., Pirila E., et al. (2000). Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions. J Pathol (in press).
