Flavonoids modulate regenerative-related cellular events in LPS-challenged dental pulp cells

Autor(es)

Soares, Igor Paulino Mendes ; Anselmi, Caroline ; Ribeiro, Rafael Antonio de Oliveira ; Mota, Rafaella Lara Maia ; Pires, Maria Luiza Barucci Araujo ; Fernandes, Lidia de Oliveira ; Costa, Carlos Alberto de Souza ; Hebling, Josimeri

• Tipo de documento: Artigo Científico
• Fonte: Journal of Dentistry; v. 151, p. 9-pg., 2024-10-30.

Resumo

Objective: To investigate the effects of quercetin (QU), hesperetin (HT), and taxifolin (TX) on human dental pulp cells (hDPCs) chronically exposed to lipopolysaccharide (LPS). Methods: First, the cytotoxicity (alamarBlue) and bioactivity (biomineralization, Alizarin Red) of QU, HT, and TX concentrations were evaluated on healthy hDPCs. Then, the effects of non-cytotoxic and bioactive concentrations were investigated on hDPCs after previous stimulation with E. coli LPS (10 mu g/mL) for 7 days. Cell culture media with and without LPS were used as positive and negative controls, respectively. Cell viability (alamarBlue), NF kappa B activation (immunofluorescence), reactive oxygen species production (ROS, H2DCFDA probe), cell migration (Transwell), inflammation-related gene expression (RT-qPCR), and odontogenic differentiation (RT-qPCR and alizarin red) were evaluated (n = 8). Data were analyzed using confidence intervals and ANOVA (alpha = 5 %). Results: The concentrations of 20 mu M QU, 20 mu M HT, and 200 mu M TX reduced cell viability by more than 30 %. The 5 mu M QU, 10 mu M HT, and 100 mu M TX concentrations were cytocompatible and stimulated biomineralization by healthy hDPCs. These concentrations were tested under the LPS challenge, and cell viability and odontogenic differentiation were significantly increased, while ROS production and inflammatory response were significantly decreased. In addition, the flavonoids significantly stimulated cell migration, reduced NF-kappa B activation, and increased biomineralization by LPS-challenged hDPCs compared to cells exposed to LPS alone and without any other treatment. Conclusion: Flavonoids can modulate the metabolism of hDPCs chronically exposed to LPS in vitro, stimulating cellular events compatible with stem cell-based regenerative processes. Clinical significance: Flavonoids may be explored as adjuvant therapeutic agents during pulp capping to counteract chronic inflammatory conditions and stimulate regeneration of the dentin-pulp complex in caries-affected teeth, thereby preserving tooth vitality. (AU)

• Processo FAPESP: 22/06603-8 - Bioatividade de flavonoides sobre células pulpares humanas sensibilizadas por lipopolissacarídeos
• Beneficiário: Rafaella Lara Maia Mota
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 19/16473-1 - Scaffolds de nanofibras de policaprolactona-nano-hidroxiapatita para regeneração do complexo dentino-pulpar: síntese, caracterização e avaliação em cultura de dentes humanos
• Beneficiário: Josimeri Hebling Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/04465-0 - Scaffolds fibrilares carregados com flavonoide para modular a resposta inflamatória e a dentinogênese em terapia pulpar vital: análises físico-químicas e biológicas
• Beneficiário: Igor Paulino Mendes Soares
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 21/13096-2 - Bioatividade de flavonoides sobre células pulpares humanas sensibilizadas por LPS e associação com scaffolds fibrilares para modulação da dentinogênese em ambiente inflamatório degenerativo
• Beneficiário: Igor Paulino Mendes Soares
• Modalidade de apoio: Bolsas no Brasil - Doutorado