Response of immortalized murine desminopathy myoblasts to altered gravitational loading

Kurzfassung

Life on Earth has evolved under the direct influence of gravity. This natural phenomenon affects almost all biological, chemical and physical processes on the molecular, cellular as well as organismic level. In view of this, already planned Space flights to the Moon are soon taking place and flights to Mars are in the process of being carried out in the near future. Notably, the gravitational loading on those planets is far beneath the gravitational loading on Earth of 1g (Moon 0.17g, Mars 0.38g). Therefore, this variation of gravitational loading is expected to lead to various severe physiological changes within organisms. Largely depending on the duration under altered gravity conditions in low Earth orbit (ISS ~420 km altitude), it has been widely recognized that there is a non-negligible loss of bone and muscle mass predominantly in the weight bearing bones and their supporting skeletal muscles, found in astronauts after space missions, harming the functional integrity of the musculoskeletal system. The space environment is defined by radiation, vacuum, magnetic fields and microgravity conditions. The two main forces acting on the human body during space flights are hyper- and microgravity conditions. During take-off as well as during landing, up to 10xg have a direct impact on the human body. Once astronauts are in orbit, the body is embedded in a very low gravity environment called microgravity (10-6g). Instantly, a change from permanent mechanical strain on the muscle to almost negligible mechanical strain can be recognized. After a few days of exposure to microgravity, distinctive muscle atrophy begins in astronauts, as well as in subjects of bed rest studies. In the scope of this work, the intermediate filament desmin and its human disorder associated disease desminopathy is investigated. Desminopathy is characterized as a very rare inherited disease belonging to the myofibrillar myopathies, which directly affect the skeletal and cardiac muscles. Keeping that in mind, the main aim of this study was to investigate whether a comparable pathological picture can be detected by mechanical overload in hyper- or by complete reduction of the mechanical load in a fast-rotating 2-D clinostat under simulated µg- conditions. To investigate the impact of different gravitational loading with the morphology of desminopathy, murine wild type myoblasts were compared with homozygous desmin knock-out myoblasts. The results show that while the effect of microgravity leads to a disruption of myotube formation as well as a defective myofibrillar apparatus in wild type cells comparable to the findings in myoblasts lacking desmin. Hypergravity, however does not affect the formation of myotubes at all.