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Inhibition of MEK1/2 Signaling Pathway Limits M2 Macrophage Polarization and Interferes in the Dental Socket Repair Process in Mice

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Autor(es):
Fonseca, Angelica Cristina ; Colavite, Priscila Maria ; Azevedo, Michelle de Campos Soriani ; Passadori, Daniela Carignatto ; Melchiades, Jessica Lima ; Ortiz, Rafael Carneiro ; Rodini, Camila Oliveira ; Trombone, Ana Paula Favaro ; Garlet, Gustavo Pompermaier
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: BIOLOGY-BASEL; v. 14, n. 2, p. 22-pg., 2025-02-01.
Resumo

Dental socket repair theoretically involves a constructive inflammatory immune response, which evolves from an initial M1 prevalence to a subsequent M2 dominance. In this scenario, the MEK1/2 signaling pathway is allegedly involved in M2 polarization. This study aimed to evaluate the impact of MEK1/2 pharmacological inhibition in the local host response and repair outcome. C57Bl/6-WT 8-week-old male mice were submitted to the extraction of the right upper incisor and treated (or not, control group) with MEK1/2 inhibitor PD0325901 (10 mg/kg/24 h/IP, MEK1/2i group) and analyzed at 0, 3, 7, and 14 days using microcomputed tomography, histomorphometry, birefringence, immunohistochemistry, and PCR array analysis. The results demonstrate that MEK1/2 inhibition limits the development of M2 response over time, being associated with lower expression of M2, MSCs, and bone markers, lower levels of growth and osteogenic factors, along with a higher expression of iNOS, IL-1b, IL-6, and TNF-alpha, as well inflammatory chemokines, indicating a predominantly M1 pro-inflammatory environment. This modulation of local inflammatory immune response is associated with impaired bone formation as demonstrated by microtomographic and histomorphometric data. The results show that MEK1/2 inhibition delays bone repair after tooth extraction, supporting the concept that M2 macrophages are essential elements for host response regulation and proper repair. (AU)

Processo FAPESP: 18/10177-9 - Análise do impacto da inibição de MEK1/2 e STAT6 na polarização de macrófagos para perfil M2, e sua influência no processo de reparo alveolar pós-exodontia em camundongos.
Beneficiário:Angelica Cristina Fonseca
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 15/24637-3 - MSCs e M2 como determinantes da natureza construtiva ou destrutiva de microambientes inflamatórios associados ao tecido ósseo
Beneficiário:Gustavo Pompermaier Garlet
Modalidade de apoio: Auxílio à Pesquisa - Temático