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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
Author(s) -
Hernández Ríos Marcela,
Sorsa Timo,
Obregón Fabián,
Tervahartiala Taina,
Valenzuela María Antonieta,
Pozo Patricia,
Dutzan Nicolás,
Lesaffre Emmanuel,
Molas Marek,
Gamonal Jorge
Publication year - 2009
Publication title -
journal of clinical periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.456
H-Index - 151
eISSN - 1600-051X
pISSN - 0303-6979
DOI - 10.1111/j.1600-051x.2009.01488.x
Subject(s) - matrix metalloproteinase , periodontitis , zymography , chronic periodontitis , bone resorption , tissue inhibitor of metalloproteinase , gelatinase , medicine , gelatinase a , mmp9 , gelatinases , metalloproteinase , resorption , pathology , chemistry , downregulation and upregulation , biochemistry , gene
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.