Muscle/bone interaction has been recently noted. Extracellular vesicles (EVs) play a vital role in physiological and pathophysiological processes by transferring microRNA (miRNA) to distant tissues. We previously reported that EVs secreted from C2C12 myoblasts (Myo-EVs) suppress osteoclast differentiation. In the present study, we identified 4 miRNAs in Myo-EVs that suppressed osteoclast-like cell formation in Raw264.7 cells using small RNA sequencing analysis. Among them, miR-196a-5p expression was higher in C2C12 cells compared to mouse osteoblasts and bone marrow cells. Transfection of miR-196a-5p mimic suppressed the mRNA levels of osteoclast-related genes and mitochondrial energy metabolism induced by receptor activator of nuclear factor-κB ligand in Raw264.7 cells. In contrast, miR-196a-5p mimic enhanced osteoblastic differentiation in ST-2 cells and MC3T3-E1 cells. In conclusion, we demonstrated that miR-196-5p suppresses osteoclast-like cell formation and mitochondrial energy metabolism in mouse cells, suggesting that it might be a crucial factor for muscle/bone interaction via EVs.

最近注意到肌肉/骨骼相互作用。细胞外囊泡 (EV) 通过将微小 RNA (miRNA) 转移到远处组织，在生理和病理生理过程中发挥着至关重要的作用。我们之前报道过 C2C12 成肌细胞 (Myo-EVs) 分泌的 EVs 抑制破骨细胞分化。在本研究中，我们使用小 RNA 测序分析鉴定了 Myo-EV 中的 4 种 miRNA，它们抑制了 Raw264.7 细胞中破骨细胞样细胞的形成。其中，与小鼠成骨细胞和骨髓细胞相比，C2C12 细胞中 miR-196a-5p 的表达更高。miR-196a-5p 模拟物的转染抑制了破骨细胞相关基因的 mRNA 水平和由核因子-κB 配体受体激活剂在 Raw264.7 细胞中诱导的线粒体能量代谢。相比之下，miR-196a-5p 模拟增强 ST-2 细胞和 MC3T3-E1 细胞中的成骨细胞分化。总之，我们证明 miR-196-5p 抑制小鼠细胞中破骨细胞样细胞的形成和线粒体能量代谢，表明它可能是通过 EV 进行肌肉/骨骼相互作用的关键因素。