MicroRNA-196a-5p in Extracellular Vesicles Secreted from Myoblasts Suppresses Osteoclast-like Cell Formation in Mouse Cells
MicroRNA-196a-5p in Extracellular Vesicles Secreted from Myoblasts Suppresses Osteoclast-like Cell Formation in Mouse Cells
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DOI：
10.1007/s00223-020-00772-6
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发表时间：
2020-10-22
影响因子：
4.2
通讯作者：
Kaji, Hiroshi
中科院分区：
文献类型：
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作者：
Takafuji, Yoshimasa;Tatsumi, Kohei;Kaji, Hiroshi
最近注意到肌肉/骨骼相互作用。细胞外囊泡（extracellular vesicles，EVs）通过将微小RNA（microRNA，miRNA）转移到远处组织中，在生理和病理生理过程中发挥重要作用。我们以前报道过C2 C12成肌细胞分泌的EV（Myo-EV）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中抑制Raw 264.7细胞中破骨细胞样细胞形成的4种miRNA。其中，miR-196 a-5 p在C2 C12细胞中的表达高于小鼠成骨细胞和骨髓细胞。转染miR-196 a-5 p模拟物可抑制Raw 264. 7细胞中破骨细胞相关基因的mRNA水平和核因子-κ B配体受体激活剂诱导的线粒体能量代谢。相比之下，miR-196 a-5 p模拟物增强ST-2细胞和MC 3 T3-E1细胞中的成骨细胞分化。总之，我们证明了miR-196- 5 p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，这表明它可能是通过EV进行肌肉/骨骼相互作用的关键因素。
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-kappa B 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.