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Proteolytic Roles of Matrix Metalloproteinase (MMP)-13 During Progression of Chronic Periodontitis: Initial Evidence for MMP-13/MMP-9 Activation Cascade

Proteolytic Roles of Matrix Metalloproteinase (MMP)-13 During Progression of Chronic Periodontitis: Initial Evidence for MMP-13/MMP-9 Activation Cascade

Marcela Hernández Ríos, Timo Sorsa, Fabián Obregón, Taina Tervahartiala, María Antonieta Valenzuela, Patricia Pozo, Nicolás Dutzan, Emmanuel Lesaffre, Marek Molas, Jorge Gamonal

J Clin Periodontol. 2009 Dec;36(12):1011-7.

PMID: 19929954

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP307002717	CL-82198		307002-71-7	Price

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