miR125a attenuates BMSCs apoptosis via the MAPK‐ERK pathways in the setting of craniofacial defect reconstruction

Abstract Bone mesenchymal stem cell (BMSC)‐based regenerative therapy is critical for the craniofacial defect reconstruction. However, oxidative stress microenvironment after transplantation limits the therapeutic efficiency of BMSC. The miR‐181c has been found to be associated with cell survival and proliferation. Herein, we investigated whether prior miR‐181c treatment promoted BMSC proliferation and survival under oxidative stress injury. The results in our study demonstrated that hydrogen peroxide (H 2 O 2 ) treatment reduced BMSC viability and this effect could be reversed via additional supplementation of miR181‐c. Mechanistically, oxidative stress increased cell apoptosis, augmented caspase‐3 activity, promoted reactive oxygen species synthesis, impaired mitochondrial potential, and induced mitochondrial dynamics imbalance. However, miR‐181c pretreatment reversed these effects of oxidative stress on BMSC. Moreover, miR‐181c treatment improved BMSC proliferation, migration and paracrine, which are very important for craniofacial reconstruction. In addition, we identified that AMP‐activated protein kinase (AMPK)–mitofusins‐1 (Mfn1) axis was the direct targets of miR‐181c in BMSC. Mfn1 silencing impaired the protective effects miR‐181c on BMSC viability and proliferation under oxidative stress environment. Collectively, our results indicate that miR‐181c participates in oxidative stress‐mediated BMSC damage by modulating the AMPK–Mfn1 signaling pathway, suggesting miR‐181c–AMPK–Mfn1 axis may serves as novel therapeutic targets to facilitate craniofacial defect reconstruction.