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

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

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/...

Full description

Saved in:
Bibliographic Details
Main Authors: Angélica Cristina Fonseca, Priscila Maria Colavite, Michelle de Campos Soriani Azevedo, Daniela Carignatto Passadori, Jessica Lima Melchiades, Rafael Carneiro Ortiz, Camila Oliveira Rodini, Ana Paula Favaro Trombone, Gustavo Pompermaier Garlet
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biology
Subjects:
osteoimmunology
bone repair
MAP kinase signaling system
Online Access:https://www.mdpi.com/2079-7737/14/2/107
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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-α, 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.
ISSN:2079-7737

Similar Items