Modulatory effect of curcumin analogs on the activation of metalloproteinases in human periodontal stem cells

Periodontitis progresses due to increased levels of active metalloproteinases (MMPs) and the imbalance between MMPs and their tissue inhibitors (TIMPs). Natural curcumin limits the lytic activity of MMPs 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 μM. At a concentration of 10 μM, 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 MMPs 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.