Proteolytic roles of matrix metalloproteinase (MMP)‐13 during progression of chronic periodontitis: initial evidence for MMP‐13/MMP‐9 activation cascade |
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| Authors: | Marcela Hernández Ríos Timo Sorsa Fabián Obregón Taina Tervahartiala María Antonieta Valenzuela Patricia Pozo Nicolás Dutzan Emmanuel Lesaffre Marek Molas Jorge Gamonal |
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| Institution: | 1. Periodontal Biology Laboratory, Faculty of Dentistry, University of Chile, Santiago, Chile;2. Pathology Department, Faculty of Dentistry, University of Chile, Santiago, Chile;3. Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Institute of Dentistry, University of Helsinki, Helsinki, Finland;4. Biochemistry and Molecular Biology Department, Faculty of Chemistry and Pharmaceutical Sciences, University of Chile, Santiago, Chile;5. Faculty of Sciences, Northern Catholic University, Antofagasta, Chile;6. Department of Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands;7. Biostatistical Centre, Catholic University of Leuven, Leuven, Belgium |
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| 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. |
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| Keywords: | chronic periodontitis progression ICTP MMP‐9 MMP‐13 |
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