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

Autor: Hernández Ríos, Marcela, Sorsa, Timo, Obregón, Fabián, Tervahartiala, Taina, Valenzuela, María Antonieta, Pozo, Patricia, Dutzan, Nicolás, Lesaffre, Emmanuel, Molas, Marek, Gamonal, Jorge
Předmět:
Zdroj: Journal of Clinical Periodontology; Dec2009, Vol. 36 Issue 12, p1011-1017, 7p, 1 Black and White Photograph, 1 Diagram, 3 Charts, 1 Graph
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
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