Regulatory roles of miR-22/Redd1-mediated mitochondrial ROS and cellular autophagy in ionizing radiation-induced BMSC injury.

Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/Redd1 pathway-mediated mitochondrial reactive oxygen species (ROS) and cellular autophagy in IR-induced apoptosis of BMSCs was determined. IR facilitated the generation and accumulation of mitochondrial ROS, which promoted IR-induced apoptosis in BMSCs; meanwhile, cellular autophagy activated by IR hold a prohibitive role on the apoptosis program. The expression of miR-22 significantly increased in BMSCs after IR exposure within 24 h. Overexpression of miR-22 evidently accelerated IR-induced accumulation of mitochondrial ROS, whereas attenuated IR stimulated cellular autophagy, thus advancing cellular apoptosis. Furthermore, we verified Redd1 as a novel target for miR-22 in rat genome. Redd1 overexpression attenuated the regulatory role of miR-22 on mitochondrial ROS generation and alleviated the inhibitive role of miR-22 on cell autophagy activated by IR, thus protecting BMSCs from miR-22-mediated cell injury induced by IR exposure. These results confirmed the role of miR-22/Redd1 pathway in the regulation of IR-induced mitochondrial ROS and cellular autophagy, and subsequent cellular apoptosis.

Radiation Induces Apoptosis and Osteogenic Impairment through miR-22-Mediated Intracellular Oxidative Stress in Bone Marrow Mesenchymal Stem Cells.

Bone marrow mesenchymal stem cells (BMSCs) were characterized by their multilineage potential and were involved in both bony and soft tissue repair. Exposure of cells to ionizing radiation (IR) triggers numerous biological reactions, including reactive oxygen species (ROS), cellular apoptosis, and impaired differentiation capacity, while the mechanisms of IR-induced BMSC apoptosis and osteogenic impairment are still unclear. Through a recent study, we found that 6 Gy IR significantly increased the apoptotic ratio and ROS generation, characterized by ROS staining and mean fluorescent intensity. Intervention with antioxidant (NAC) indicated that IR-induced cellular apoptosis was partly due to the accumulation of intracellular ROS. Furthermore, we found that the upregulation of miR-22 in rBMSCs following 6 Gy IR played an important role on the ROS generation and subsequent apoptosis. In addition, we firstly demonstrated that miR-22-mediated ROS accumulation and cell injury had an important regulated role on the osteogenic capacity of BMSCs both in vitro and in vivo. In conclusion, IR-induced overexpression of miR-22 regulated the cell viability and differentiation potential through targeting the intracellular ROS.