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Extracellular vesicles secreted from mouse muscle cells suppress osteoclast formation: Roles of mitochondrial energy metabolism
Bone ( IF 4.1 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.bone.2020.115298
Yoshimasa Takafuji , Kohei Tatsumi , Masayoshi Ishida , Naoyuki Kawao , Kiyotaka Okada , Hiroshi Kaji

Recent reports have described the interactions of muscle and bone. Various muscle-derived humoral factors, known as myokines, affect bone. Although extracellular vesicles (EVs) play a vital role in physiological and pathophysiological processes by transferring their contents to distant tissues during bone metabolism, the roles of EVs in the muscle-bone interactions remain unknown. In the present study, we investigated the effects of EVs secreted from mouse muscle C2C12 cells on mouse bone cells and mitochondrial biogenesis. EVs secreted from C2C12 cells (Myo-EVs) were isolated from the conditioned medium of C2C12 cells by ultracentrifugation. Myo-EVs suppressed osteoclast formation as well as the expression of tartrate-resistant acid phosphatase, cathepsin K, nuclear factor of activated T-cells cytoplasmic 1 and dendritic cell-specific transmembrane protein induced by receptor activator of nuclear factor κB ligand (RANKL) in mouse bone marrow cells and preosteoclastic Raw264.7 cells. Moreover, Myo-EVs suppressed oxygen consumption and mRNA expression of the mitochondrial biogenesis markers enhanced by RANKL in these cells. However, Myo-EVs did not affect the phenotypes or mitochondrial biogenesis of mouse primary osteoblasts. In conclusion, the present study showed for the first time that Myo-EVs suppress osteoclast formation and mitochondrial energy metabolism in mouse bone marrow and Raw264.7 cells. EVs secreted from skeletal muscles might be a crucial mediator of muscle-bone interactions.

中文翻译:

小鼠肌肉细胞分泌的细胞外囊泡抑制破骨细胞的形成:线粒体能量代谢的作用

最近的报告描述了肌肉和骨骼的相互作用。各种肌肉衍生的体液因子,称为肌动因子,会影响骨骼。尽管细胞外囊泡 (EVs) 在骨代谢过程中通过将其内容物转移到远处组织而在生理和病理生理过程中发挥重要作用,但 EVs 在肌肉 - 骨骼相互作用中的作用仍然未知。在本研究中,我们研究了小鼠肌肉 C2C12 细胞分泌的 EVs 对小鼠骨细胞和线粒体生物发生的影响。通过超速离心从 C2C12 细胞的条件培养基中分离出 C2C12 细胞分泌的 EV(Myo-EV)。Myo-EVs 抑制破骨细胞的形成以及抗酒石酸酸性磷酸酶、组织蛋白酶 K、小鼠骨髓细胞和破骨细胞 Raw264.7 细胞中核因子 κB 配体受体激活剂 (RANKL) 诱导的活化 T 细胞胞质 1 和树突细胞特异性跨膜蛋白的核因子。此外,Myo-EVs 抑制了这些细胞中由 RANKL 增强的线粒体生物发生标志物的氧消耗和 mRNA 表达。然而,Myo-EVs 不影响小鼠原代成骨细胞的表型或线粒体生物发生。总之,本研究首次表明,Myo-EVs 抑制小鼠骨髓和 Raw264.7 细胞中破骨细胞的形成和线粒体能量代谢。从骨骼肌分泌的 EV 可能是肌肉-骨骼相互作用的关键介质。
更新日期:2020-05-01
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