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

Abstract

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.

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy

“…One study found that radiation induced apoptosis of BMSCs through mir-22-exotrophic stress, which affected the repair and regeneration of bone tissue in irradiated sites [Liu et al, 2018].…”

“…In the process of apoptosis, the cell elastic modulus and volume significantly decreased, and the cell surface roughness obviously increased; subsequently, the early apoptosis marker PS was detected, eventually the cells died. In combination with the previous molecular mechanism of stem cell apoptosis [Tower, 2015;Liu et al, 2018;Sun et al, 2018;Chen et al, 2015;Cui, 2007], stem cell apoptosis is not only a biological apoptotic signal cascade process, but is also accompanied by the reconstruction of mechanics and nanomorphology. These findings were helpful for further understanding and mastering the apoptosis of cells from the perspective of mechanics.…”

Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway

“…This may be explained due to the multifunction of this natural compound as follows: first, SAL may serve as a direct inhibitor on miR-22 formation, while the detailed mechanisms remain to be further explored. Second, miR-22 induces cellular senescence accompanied with oxidative stress and itself per se could mediate the intracellular oxidative stress [47][48][49], and SAL may directly prevent this process as it is a potent antioxidant according to our previous work and others' [21,39]. Third, SAL could rescue the declined SIRT1 by other pathways.…”

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy

“…In the process of apoptosis, the cell elastic modulus and volume significantly decreased, and the cell surface roughness obviously increased; subsequently, the early apoptosis marker PS was detected, eventually the cells died. In combination with the previous molecular mechanism of stem cell apoptosis [Tower, 2015; Liu et al, 2018; Sun et al, 2018; Chen et al, 2015; Cui, 2007], stem cell apoptosis is not only a biological apoptotic signal cascade process, but is also accompanied by the modification of cell mechanics and nanomorphology. This study is helpful for further understanding and mastering the apoptosis of cells from the perspective of mechanics.…”

“…However, abnormal apoptosis of stem cells can lead to disease and/or poor self-repairing capability of the body. One study found that radiation induced apoptosis of BMSCs through mir-22-exotrophic stress, which affected the repair and regeneration of bone tissue in irradiated sites [Liu et al, 2018]. Moreover, the major metabolite 2,5-hexanedione of the organic solvent n-hexane, which is widely used in adhesive preparation, paints, varnishes, oil-based paint, and the food industry, can induce apoptosis of BMSCs via the mitochondria-mediated caspase-3 pathway [Sun et al, 2018; Chen et al, 2015] and nervous lesions [Cui et al, 2007].…”