Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade.
OBJECTIVE
Matrix metalloproteinases (MMP)-13 can initiate bone resorption and activate proMMP-9 in vitro, and both these MMPs have been widely implicated in tissue destruction associated with chronic periodontitis. We studied whether MMP-13 activity and TIMP-1 levels in gingival crevicular fluid (GCF) associated with progression of chronic periodontitis assessed clinically and by measuring carboxy-terminal telopeptide of collagen I (ICTP) levels. We additionally addressed whether MMP-13 could potentiate gelatinase activation in diseased gingival tissue.


METHODS
In this prospective study, GCF samples from subjects undergoing clinical progression of chronic periodontitis and healthy controls were screened for ICTP levels, MMP-13 activity and TIMP-1. Diseased gingival explants were cultured, treated or not with MMP-13 with or without adding CL-82198, a synthetic MMP-13 selective inhibitor, and assayed by gelatin zymography and densitometric analysis.


RESULTS
Active sites demonstrated increased ICTP levels and MMP-13 activity (p<0.05) in progression subjects. The MMP-9 activation rate was elevated in MMP-13-treated explants (p<0.05) and MMP-13 inhibitor prevented MMP-9 activation.


CONCLUSIONS
MMP-13 could be implicated in the degradation of soft and hard supporting tissues and proMMP-9 activation during progression of chronic periodontitis. MMP-13 and -9 can potentially form an activation cascade overcoming the protective TIMP-1 shield, which may become useful for diagnostic aims and a target for drug development.
Hernández Ríos
Marcela
M
Periodontal Biology Laboratory, Faculty of Dentistry, University of Chile, Santiago, Chile. mhernandezrios@gmail.com
Sorsa
Timo
T
Obregón
Fabián
F
Tervahartiala
Taina
T
Valenzuela
María Antonieta
MA
Pozo
Patricia
P
Dutzan
Nicolás
N
Lesaffre
Emmanuel
E
Molas
Marek
M
Gamonal
Jorge
J
D000328:Adult; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000201:enzymology*; D024042:Collagen Type I / Q000032:analysis; D018450:Disease Progression; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D005883:Gingival Crevicular Fluid / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010455:Peptides / Q000032:analysis; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
D024042:Collagen Type I; D004792:Enzyme Precursors; D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; C052929:collagen type I trimeric cross-linked peptide; D053509:Matrix Metalloproteinase 13; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9