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Modulatory effect of curcumin analogs on the activation of metalloproteinases in human periodontal stem cells
Author(s) -
Boșca Adina B.,
Ilea Aranka,
Sorițău Olga,
Tatomir Corina,
Miklášová Natalia,
Pârvu Alina E.,
Mihu Carmen M.,
Melincovici Carmen S.,
FischerFodor Eva
Publication year - 2019
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12625
Subject(s) - curcumin , periodontal fiber , matrix metalloproteinase , chemistry , cytotoxicity , periodontal ligament stem cells , stem cell , in vitro , pharmacology , periodontitis , dental alveolus , biochemistry , dentistry , microbiology and biotechnology , enzyme , medicine , biology , alkaline phosphatase
Periodontitis progresses due to increased levels of active metalloproteinases ( MMP s) and the imbalance between MMP s and their tissue inhibitors ( TIMP s). Natural curcumin limits the lytic activity of MMP s but has low cellular uptake. Use of synthetic curcumin analogs could be a means of overcoming this limitation of treatment efficiency. Human periodontal stem cells were isolated from gingival tissue, gingival ligament fibers, periodontal ligament, and alveolar bone. The effect of five synthetic curcumin analogs was compared with that of natural curcumin by assessing cytotoxicity [by 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazolium bromide ( MTT ) assay], the cellular uptake (by fluorometry), the proteolytic activities of MMP ‐2 and ‐9 (by zymography), and the levels of TIMP ‐1 (by ELISA ). Our results indicated increased cytotoxicity of synthetic curcumins for doses between 100 and 250 μ M. At a concentration of 10 μ M, cellular uptake of synthetic curcumins varied depending on their chemical structure. The curcumin compounds modulated pro‐ MMP ‐2 levels and increased TIMP ‐1 production. There was no detectable synthesis of pro‐ MMP ‐9 and no activation of MMP s 2 and 9. Gingival tissue and gingival ligament fiber stem cells were most responsive to treatment, showing inverse correlations between pro‐ MMP ‐2 and TIMP ‐1 levels. In conclusion, synthetic curcumins influenced the balance between pro‐ MMP ‐2 and TIMP ‐1 in human periodontal stem cells in vitro , and this could open perspectives for their application as adjuvants in periodontal therapy.