Mek1/2 Blockade Results In Altered Inflammatory Response And Delayed Alveolar Bone Repair

Abstract M1 and M2 macrophages play an important modulating role in tissue repair. In alveolar bone repair, the determinant these different phenotypes acquisition and its impact in repair process remains undefined, with a current assumption that assuming M2 conversion contributes to repair resolution. Considering MEK1/2 signaling pathway as a determinant for M2 polarization, the objective of this project was to evaluate the effect of MEK1/2 pharmacological inhibition in the local host response and repair outcome. C57Bl/6 (WT) mice, treated with MEK1/2i inhibitor PD0325901 (10mg/kg/24h/IP), which underwent extraction of the right upper incisor and, subsequently analyzed by computed microtomography (uCt) and histomorphometric analysis. uCt analysis, performed at 0,3,7 and 14 days periods revealed an overall smaller bone volume in MEK1/2i group, with a statistical difference in 14 days (p<0,05 MEK1/2i versus Control). These results, when combined with the histomorphometric analysis, reveals a delay in the alveolar bone repair process in the MEK1/2i group, characterized at 7 days by a higher density of connective tissue parameters, specifically collagen fibers, blood vessels, inflammatory cells and blood clot, when compared with control group. Additionally, a lower density of bone tissue parameters, specifically osteoblasts, osteoclasts and bone matrix, where observed upon MEK1/2i inhibition. Therefore, partially, the results show that MEK1/2 inhibitory effect results in delayed alveolar bone repair, initially involving the control of inflammatory cell migration and subsequent bone formation. Supported by grants from FAPESP (2018/10177-9 and 2015/24637-3)