| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 152, 1489-1499, Copyright © 1998 by American Society for Investigative Pathology
REGULAR ARTICLES |
VJ Uitto, K Airola, M Vaalamo, N Johansson, EE Putnins, JD Firth, J Salonen, C Lopez-Otin, U Saarialho-Kere and VM Kahari
Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, Canada. jukka@unixg.ubc.ca
Increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells. Here we have studied, whether collagenase-3 (MMP-13), a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity, is expressed in the epithelium of chronically inflamed mucosa. Examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP-13 in basal cells of some epithelial rete ridges expanding into connective tissue. Immunohistochemical staining demonstrated that these cells also expressed strongly laminin-5, suggesting that they are actively migrating cells. A strong signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket, whereas no collagenase-1 (MMP-1) mRNA was detected in any areas of the epithelium. MMP-13 expression was also detected in fibroblast-like cells associated with collagen fibers of the inflamed subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens. Regulation of MMP-13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament. In these cells, MMP-13 expression at the mRNA and protein level was potently enhanced (up to sixfold) by tumor necrosis factor-alpha, transforming growth factor-beta(1), and transforming growth factor-alpha and by keratinocyte growth factor in the presence of heparin. In addition, plating periodontal ligament epithelial cells on type I collagen stimulated MMP-13 expression (sevenfold) as compared with cells grown on tissue culture plastic. The results of this study show, that expression of MMP-13 is specifically induced in undifferentiated epithelial cells during chronic inflammation due to exposure to cytokines and collagen. Thus, it is likely that MMP-13 expression is instrumental in the subepithelial collagenolysis and local invasion of the activated mucosal epithelium into the connective tissue.
This article has been cited by other articles:
 |
|
 |
|
  J. S KINNEY, C. A RAMSEIER, and W. V GIANNOBILE Oral Fluid-Based Biomarkers of Alveolar Bone Loss in Periodontitis Ann. N.Y. Acad. Sci., March 1, 2007; 1098(1): 230 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.M. Golub, J.B. Payne, R.A. Reinhardt, and G. Nieman Can Systemic Diseases Co-induce (Not Just Exacerbate) Periodontitis? A Hypothetical "Two-hit" Model J. Dent. Res., February 1, 2006; 85(2): 102 - 105. [Full Text] [PDF]
|
|
|
|
 |
|
 V.-J. Uitto, D. Baillie, Q. Wu, R. Gendron, D. Grenier, E. E. Putnins, A. Kanervo, and J. D. Firth Fusobacterium nucleatum Increases Collagenase 3 Production and Migration of Epithelial Cells Infect. Immun., February 1, 2005; 73(2): 1171 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Yang, C.-S. Chien, C.-C. Yao, L.-D. Hsiao, Y.-C. Huang, and C. B. Wu Mechanical Strain Induces Collagenase-3 (MMP-13) Expression in MC3T3-E1 Osteoblastic Cells J. Biol. Chem., May 21, 2004; 279(21): 22158 - 22165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Putnins, A.-R. Sanaie, Q. Wu, and J. D. Firth Induction of Keratinocyte Growth Factor 1 Expression by Lipopolysaccharide Is Regulated by CD-14 and Toll-Like Receptors 2 and 4 Infect. Immun., December 1, 2002; 70(12): 6541 - 6548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hintermann, S. K. Haake, U. Christen, A. Sharabi, and V. Quaranta Discrete Proteolysis of Focal Contact and Adherens Junction Components in Porphyromonas gingivalis-Infected Oral Keratinocytes: a Strategy for Cell Adhesion and Migration Disabling Infect. Immun., October 1, 2002; 70(10): 5846 - 5856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Ware and M. A. Matthay Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L924 - L940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V.-J. Uitto, J.I. Salonen, J.D. Firth, H. Jousimies-Somer, and U. Saarialho-Kere Matrilysin (Matrix Metalloproteinase-7) Expression in Human Junctional Epithelium J. Dent. Res., April 1, 2002; 81(4): 241 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Nielsen, F. Rank, J. M. Lopez, M. Balbin, F. Vizoso, L. R. Lund, K. Dano, and C. Lopez-Otin Collagenase-3 Expression in Breast Myofibroblasts as a Molecular Marker of Transition of Ductal Carcinoma in Situ Lesions to Invasive Ductal Carcinomas Cancer Res., October 1, 2001; 61(19): 7091 - 7100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Brinckerhoff, J. L. Rutter, and U. Benbow Interstitial Collagenases as Markers of Tumor Progression Clin. Cancer Res., December 1, 2000; 6(12): 4823 - 4830. [Abstract] [Full Text]
|
|
|
|
 |
|
 T Etoh, H Inoue, Y Yoshikawa, G F Barnard, S Kitano, and M Mori Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness Gut, July 1, 2000; 47(1): 50 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Johansson, R Ala-aho, V Uitto, R Grenman, N. Fusenig, C Lopez-Otin, and V. Kahari Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase J. Cell Sci., January 1, 2000; 113(2): 227 - 235. [Abstract] [PDF]
|
|
|
|
|
|
L. Ravanti, L. Hakkinen, H. Larjava, U. Saarialho-Kere, M. Foschi, J. Han, and V.-M. Kahari Transforming Growth Factor-beta Induces Collagenase-3 Expression by Human Gingival Fibroblasts via p38 Mitogen-activated Protein Kinase J. Biol. Chem., December 24, 1999; 274(52): 37292 - 37300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. GOLUB, N. S. RAMAMURTHY, A. LLAVANERAS, M. E. RYAN, H. M. LEE, Y. LIU, S. BAIN, and T. SORSA A Chemically Modified Nonantimicrobial Tetracycline (CMT-8) Inhibits Gingival Matrix Metalloproteinases, Periodontal Breakdown, and Extra-Oral Bone Loss in Ovariectomized Rats Ann. N.Y. Acad. Sci., June 30, 1999; 878(1): 290 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Sukhova, U. Schonbeck, E. Rabkin, F. J. Schoen, A. R. Poole, R. C. Billinghurst, and P. Libby Evidence for Increased Collagenolysis by Interstitial Collagenases-1 and -3 in Vulnerable Human Atheromatous Plaques Circulation, May 18, 1999; 99(19): 2503 - 2509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Romanelli, S. Mancini, C. Laschinger, C. M. Overall, J. Sodek, and C. A. G. McCulloch Activation of Neutrophil Collagenase in Periodontitis Infect. Immun., May 1, 1999; 67(5): 2319 - 2326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. WESTERMARCK and V.-M. KÄHÄRI Regulation of matrix metalloproteinase expression in tumor invasion FASEB J, May 1, 1999; 13(8): 781 - 792. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. Johansson, M. Vaalamo, S. Grenman, S. Hietanen, P. Klemi, U. Saarialho-Kere, and V.-M. Kahari Collagenase-3 (MMP-13) is Expressed by Tumor Cells in Invasive Vulvar Squamous Cell Carcinomas Am. J. Pathol., February 1, 1999; 154(2): 469 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ravanti, J. Heino, C. Lopez-Otin, and V.-M. Kahari Induction of Collagenase-3 (MMP-13) Expression in Human Skin Fibroblasts by Three-dimensional Collagen Is Mediated by p38 Mitogen-activated Protein Kinase J. Biol. Chem., January 22, 1999; 274(4): 2446 - 2455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Gillis, U Savla, O. Volpert, B Jimenez, C. Waters, R. Panos, and N. Bouck Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function J. Cell Sci., January 6, 1999; 112(12): 2049 - 2057. [Abstract] [PDF]
|
|
|
|
|
|
K. Sato, T. Ebihara, E. Adachi, S. Kawashima, S. Hattori, and S. Irie Possible Involvement of Aminotelopeptide in Self-assembly and Thermal Stability of Collagen I as Revealed by Its Removal with Proteases J. Biol. Chem., August 11, 2000; 275(33): 25870 - 25875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J.G. Jimenez, M. Balbin, J. Alvarez, T. Komori, P. Bianco, K. Holmbeck, H. Birkedal-Hansen, J. M. Lopez, and C. Lopez-Otin A regulatory cascade involving retinoic acid, Cbfa1, and matrix metalloproteinases is coupled to the development of a process of perichondrial invasion and osteogenic differentiation during bone formation J. Cell Biol., December 24, 2001; 155(7): 1333 - 1344. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
