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.

Double-edged effects and mechanisms of Zn2+ microenvironments on osteogenic activity of BMSCs: osteogenic differentiation or apoptosis

“…A recent research showed that oxidative stress increased BMSC apoptosis and impaired mitochondrial potential by promoting ROS synthesis and further inhibited proliferation, migration and paracrine of BMSC which were very important for bone reconstruction. 50 Similarly, the results of our study revealed that the high concentration (15 mg mL À1 ) of Zn 2+ , which was not conducive to osteogenesis, increased ROS generation and then impaired the adhesion, proliferation and osteogenic differentiation of rBMSCs.…”

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression

“…Ectopic expression of miR-181c is capable of limiting the proliferation of synoviocyte and expression of inflammatory factors correlated with the pathogenesis of osteoarthritis [9]. Furthermore, miR-181c accelerates BMSC proliferation and survival under oxidative stress injury [27]. However, how miR-181c-5p functioned in hUCMSC-EVs was little known based on the previous analysis.…”

The interaction of miR-181a-5p and sirtuin 1 regulated human bone marrow mesenchymal stem cells differentiation and apoptosis

“…At present, there are many studies have concluded the effects of drugs or other factors on hBMSCs apoptosis and its pro-apoptotic mechanism. Among them, it is found that apoptosis of hBMSCs is accompanied by a rise in pro-apoptotic proteins Cleaved caspase-3 as well as Bax levels, and a drop in anti-apoptotic proteins Bcl-2 levels [ 25–28 ]. Based on our work, miR-181a-5p visually stimulated cleaved caspase3 expression and inhibited the Bcl2/Bax ratio.…”