M2 macrophage-derived exosomes carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-β1

Abstract

Purpose Radiotherapy is essential to cancer treatment, while it inevitably injures the surrounding normal tissues, and bone tissue is one of the most common sites prone to irradiation. Bone marrow mesenchymal stem cells (BMMSCs) are sensitive to irradiation and the irradiated dysfunction of BMMSCs may be closely related to irradiation-induced bone damage. Macropahges paly important role in stem cell function regulation, bone metabolic balance and irradiation response, but the effects of macrophages on irradiated BMMSCs are still unclear. This study aimed to investigate the role of macrophages and macrophage-derived exosomes in restoring irradiated BMMSCs function.Methods The effects of macrophage conditioned medium (CM) and macrophage-derived exosomes on osteogenic and brogenic differentiation capacities of irradiated BMMSCs were detected. The key microribonucleic acids (miRNAs) and targeted proteins in macrophage-derived exosomes were also determined. ResultsThe results showed that X-ray irradiation signi cantly inhibited the proliferation of BMMSCs.Additionally, it caused a differentiation imbalance of BMMSCs, with decreased osteogenic differentiation and increased brogenic differentiation. M2 macrophage-derived exosomes (M2D-exos) inhibited the brogenic differentiation and promoted the osteogenic differentiation of irradiated BMMSCs. We identi ed that miR-142-3p was signi cantly overexpressed in M2D-exos and irradiated BMMSCs treated with M2D-exos. After inhibition of miR-142-3p in M2 macrophage, the effects of M2D-exos on irradiated BMMSCs differentiation were eliminated. Furthermore, transforming growth factor beta 1 (TGF-β1), as a direct target of miR-142-3p, was signi cantly decreased in irradiated BMMSCs treated by M2D-exos. ConclusionThis study indicated that M2D-exos could carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-β1. These ndings pave the way for a new, promising, and cell-free therapeutic method to treat radiation-induced bone damage.