Evaluation of inductive effects of different concentrations of cyclosporine A on MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2 in fetal and adult human gingival fibroblasts

Abstract

Background The etiology of gingival overgrowth due to cyclosporine A (CsA) is still unknown. The aim of this study was to determine the possible role of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) on extra-cellular matrix (ECM) homeostasis when treated with different levels of CsA and its difference between fetal and adult human gingival fibroblasts (HGFs). Methods Each group of cells (adult and fetal) was cultured in 40 wells that consisted of four different CsA treatment concentrations. Every 10 wells were treated with 0, 50, 100, and 150 ng/mL of CsA which makes a total of 80 wells. Supernatants of every well were used to determine the concentration of MMPs and TIMPs using the Elisa kits from Boster, CA, USA. Results MMP-1 level increased with the treatment of CsA when treated with 50 and 150 ng/mL of CsA (p = 0.02 and p = 0.04) as TIMP-1 decreased (p < 0.0001) in adult group; while in the fetal group, TIMP-1 level increased with treatment of 150 ng/mL (p < 0.0001). MMP-2 level increased in both adult and fetal groups (p < 0.0001). MMP-3 level decreased in adult group (p < 0.0001) but went up in fetal HGFs (p = 0.01) when treated with 150 ng/mL CsA. TIMP-2 level increased in all wells significantly when treated with CsA (p < 0.0001). The study showed that CsA affects secretion of MMPs and TIMPs. MMP-1 increment and TIMP-1 decrement were observed, which indicate more degradation of ECM. This may be due to single donor use in this study. TIMP-2 and MMP-2 were both more active when treated with CsA which may be due to the gelatinase activity of them and that in CsA gingival overgrowth. There was more inflammation rather than fibrosis.

Evaluation of the Effects of E-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on Human Gingival Epithelial Cells

“…MMP-1 is a key enzyme in collagen degradation, which can promote collagen degradation. 51 Our results showed that smoking tobacco and watermelon-flavored e-cigarettes significantly increased MMP1/3 levels and reduced type I collagen levels, suggesting that increased MMP-1/3 levels by smoking tobacco and watermelon-flavored e-cigarettes might degrade collagen levels and contribute to the bleeding gum and other diseases. Thus, some flavored e-cigarettes may also have an adverse effect on the mouth.…”

Salivary Oxidative Stress Markers’ Relation to Oral Diseases in Children and Adolescents

“…Nonetheless, these bacteria and plaque are a part of the inflammation process which contributes to periodontal disease and dental caries originally, and thus can affect the production of oxidative stress markers, but to what extent is still unknown. Interestingly, in adolescents (13)(14)(15)(16)(17)(18) the plaque index increased in the CI = 2 group almost significantly (p = 0.05) and in the children's (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) group, it had an insignificant increase. Further studies are needed in order to be able to determine the level of effect that plaques can have on this matter.…”

“…Periodontal disease is another frequent oral problem-11% of the global population are suffering from it [3]. Bacteria can cause dental caries and periodontal problems; however, both diseases have a multifactorial etiology, with different biomarkers, that affect saliva [1,4,5]. From these biomarkers, oxidative agents such as reactive oxygen/nitrogen substances (ROS/RNS) take part [6].…”

Colágeno tipo I en el agrandamiento gingival inducido por tratamiento ortodóntico: un estudio inmunohistoquímico piloto

“…De igual manera, modificaciones en la expresión de las metaloproteinasas de la matriz (mmp), enzimas fundamentales en la regulación de los componentes de la mec, es otro factor que podría estar implicado en el incremento de las fibras de colágeno en los tejidos gingivales de pacientes con ag portadores de ortodoncia. Algunos estudios han demostrado concentraciones bajas de mmp-1 y mmp-2 en fibroblastos gingivales de pacientes con ag (29,30). La mmp-1 es conocida como una colagenasa que degrada el colágeno intersticial, al igual que la mmp-2 (30), y aunque los mecanismos que involucran los efectos de las tensiones mecánicas sobre la proliferación y síntesis de la mec, incluyendo el colágeno tipo I, no son aún claros, un estudio que investigó los efectos de las fuerzas mecánicas sobre la proliferación de fibroblastos gingivales y la síntesis de la mec reportó un aumento significativo en la proliferación celular y la expresión de colágeno tipo I e indicó una disminución en la expresión de mmp-1.…”

“…Algunos estudios han demostrado concentraciones bajas de mmp-1 y mmp-2 en fibroblastos gingivales de pacientes con ag (29,30). La mmp-1 es conocida como una colagenasa que degrada el colágeno intersticial, al igual que la mmp-2 (30), y aunque los mecanismos que involucran los efectos de las tensiones mecánicas sobre la proliferación y síntesis de la mec, incluyendo el colágeno tipo I, no son aún claros, un estudio que investigó los efectos de las fuerzas mecánicas sobre la proliferación de fibroblastos gingivales y la síntesis de la mec reportó un aumento significativo en la proliferación celular y la expresión de colágeno tipo I e indicó una disminución en la expresión de mmp-1. En este mismo reporte, cuando los autores utilizaron un inhibidor del tgf-β1, se pudo constatar una atenuación de los efectos de las fuerzas mecánicas sobre la proliferación de fibroblastos y expresión de colágeno tipo I y la mmp-1 (31).…”