RESUMO
Periodontal ligament stem cells (PDLSCs) show plasticity towards the adipogenic lineage; however, little has been done on the participation of epigenetic mechanisms. Histone acetylation is a dynamic process, though balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) activities. This process can be halted by HDACs inhibitors, such as trichostatin A (TSA) and valproic acid (VPA). This study aimed to determine the role of HDACs class I in adipogenic differentiation of PDL cells. PDLSCs were treated with TSA at concentrations of 100, 200, and 250 nM, or VPA at 1, 4 and 8 mM. Cell viability was assessed using MTT assays. Gene expression of pluripotency markers (NANOG, OCT4, SOX2), HAT genes (p300, GCN5), and HDACs genes (HDAC1-3) was analyzed by RT-qPCR. Adipogenic differentiation was evaluated via oil red O staining, and acetylation of histone H3 lysine 9 (H3K9ac) was examined by Western blot. VPA treatment resulted in a 60% reduction in cell proliferation, compared to a 50% when using TSA. Cell viability was not affected by either inhibitor. Furthermore, both TSA and VPA induced adipogenic differentiation, through an increase in the deposition of lipid droplets and in GCN5 and p300 expression were observed. Western blot analysis showed that TSA increased H3K9ac levels on adipogenic differentiation of PDLSCs. These findings highlight the potential of HDAC inhibitors as a tool for modulating H3K9 acetylation status and thus influencing adipogenic differentiation of PDLCs.
Assuntos
Adipogenia , Diferenciação Celular , Sobrevivência Celular , Inibidores de Histona Desacetilases , Ligamento Periodontal , Ácido Valproico , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Ácido Valproico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Ácidos Hidroxâmicos/farmacologia , Células Cultivadas , Histonas/metabolismo , Proliferação de Células/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
Dental tissue stem cells (DTSCs) are well known for their multipotent capacity and regenerative potential. They also play an important role in the immune response of inflammatory processes derived from caries lesions, periodontitis, and gingivitis. These oral diseases are triggered by toxins known as lipopolysaccharides (LPS) produced by gram-negative bacteria. LPS present molecular patterns associated with pathogens and are recognized by Toll-like receptors (TLRs) in dental stem cells. In this review, we describe the effect of LPS on the biological behavior of DTSCs. We also focus on the molecular sensors, signaling pathways, and emerging players participating in the interaction of DTSCs with lipopolysaccharides. Although the scientific advances generated provide an understanding of the immunomodulatory potential of DTSCs, there are still new reflections to explore with regard to their clinical application in the treatment of oral inflammatory diseases.
