Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), Ludwig-Maximilians-University (LMU), Fraunhoferstraße 20, 82152 Planegg-Martinsried, Germany.
Faculty of Sport and Health Sciences, Technical University of Munich, Georg-Brauchle-Ring 60, 80992 Munich, Germany.
Cells. 2022 Mar 21;11(6):1059. doi: 10.3390/cells11061059.
Injuries, high altitude, and endurance exercise lead to hypoxic conditions in skeletal muscle and sometimes to hypoxia-induced local tissue damage. Thus, regenerative myoblasts/satellite cells are exposed to different levels and durations of partial oxygen pressure depending on the spatial distance from the blood vessels. To date, it is unclear how hypoxia affects myoblasts proliferation, differentiation, and particularly fusion with normoxic myoblasts. To study this, we investigated how 21% and 2% oxygen affects C2C12 myoblast morphology, proliferation, and myogenic differentiation and evaluated the fusion of normoxic- or hypoxic-preconditioned C2C12 cells in 21% or 2% oxygen in vitro. Out data show that the long-term hypoxic culture condition does not affect the proliferation of C2C12 cells but leads to rounder cells and reduced myotube formation when compared with myoblasts exposed to normoxia. However, when normoxic- and hypoxic-preconditioned myoblasts were differentiated together, the resultant myotubes were significantly larger than the control myotubes. Whole transcriptome sequencing analysis revealed several novel candidate genes that are differentially regulated during the differentiation under normoxia and hypoxia in mixed culture conditions and may thus be involved in the increase in myotube size. Taken together, oxygen-dependent adaption and interaction of myoblasts may represent a novel approach for the development of innovative therapeutic targets.
损伤、高海拔和耐力运动导致骨骼肌缺氧，并有时导致缺氧诱导的局部组织损伤。因此，再生成肌细胞/卫星细胞会根据与血管的空间距离，暴露于不同水平和持续时间的部分氧分压下。迄今为止，尚不清楚缺氧如何影响成肌细胞的增殖、分化，特别是与正常氧条件下的成肌细胞融合。为了研究这一点，我们研究了 21%和 2%的氧气如何影响 C2C12 成肌细胞的形态、增殖和肌生成分化，并评估了在 21%或 2%的氧气中体外培养的正常氧或低氧预处理 C2C12 细胞的融合情况。我们的数据表明，长期低氧培养条件不会影响 C2C12 细胞的增殖，但与正常氧条件下暴露的成肌细胞相比，会导致细胞更圆，肌管形成减少。然而，当正常氧和低氧预处理的成肌细胞一起分化时，所得的肌管明显大于对照肌管。全转录组测序分析揭示了在混合培养条件下正常氧和低氧分化过程中差异表达的几个新的候选基因，这些基因可能参与肌管大小的增加。总之，成肌细胞的氧依赖性适应和相互作用可能代表一种开发创新治疗靶点的新方法。
