Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade

• Published in: Journal of clinical periodontology Vol. 36; no. 12; pp. 1011 - 1017
• Main Authors: Hernández Ríos, Marcela, Sorsa, Timo, Obregón, Fabián, Tervahartiala, Taina, Valenzuela, María Antonieta, Pozo, Patricia, Dutzan, Nicolás, Lesaffre, Emmanuel, Molas, Marek, Gamonal, Jorge
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2009
• Subjects: Adult; Case-Control Studies; Chronic Periodontitis - enzymology; chronic periodontitis progression; Collagen Type I - analysis; Dentistry; Disease Progression; Enzyme Activation; Enzyme Precursors - metabolism; Female; Gingival Crevicular Fluid - enzymology; Humans; Hydrolysis; ICTP; Male; Matrix Metalloproteinase 13 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; Middle Aged; MMP-13; MMP-9; Peptides - analysis; Prospective Studies; Tissue Inhibitor of Metalloproteinase-1 - analysis
• ISSN: 0303-6979; 1600-051X
• DOI: 10.1111/j.1600-051X.2009.01488.x

Aim: 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. Materials and 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.