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Effect of Simulated Weightlessness on the Induction of ERK2 by Fluid Shear Stress in MG-63 Osteosarcoma Cells.    S. Zhang, B. Wang, Z. Yang and X.Q. Sun. Dept. of Aerospace Biodynamics, FMMU, Xi’an, 710032, P.R.China

Objective This study was aimed to explore the relationship of Shc and ERK in MG-63 osteosarcoma cells mechanotransduction and to survey its functional alteration in simulated weightlessness. Method One group MG-63 osteosarcoma cells were co-transfected with negative mutant of Shc (Shc-SH2) and Myc-ERK2. Another group cells were co-transfected with pcDNA3 parental plasmid together with Myc-ERK2. Then, the effects of 15 min fluid shear stress (FSS) on the induction of ERK were examined in the above cells cultured 60 h in two different gravitational environments, i.e. 1G terrestrial gravitational condition and simulated weightlessness condition. FSS was set to 1.5 Pa in the experiment and parallel control groups were set to no FSS in two gravitational condition. Results In 1G terrestrial gravitational condition, FSS caused significantly activated Myc-ERK2 in cells transfected with pcDNA3, and this FSS induction of Myc-ERK2 activity was drastically reduced in cells transfected with Shc-SH2. There was no measurable value in the amount of Myc-ERK2 activities in MG-63 cells without FSS treatment. As to the MG-63 cells cultured in simulated weightlessness by using clinostat, mechanical stimulation by 1.5 Pa FSS resulted, after 15 min, in increased amount of Myc-ERK2 activities in cells transfected with pcDNA3. And the nature of cell responsiveness was significantly different between 1G and simulated weightlessness conditions (P<0.01). Conclusion These results suggested that Shc was involved in the upstream signaling for the shear stress induction of ERK. And mechanotransduction in MG-63 cells was affected by simulated weightlessness. This abnormal mechanotransduction might contribute to osteopenia induced by weightlessness observed in crewmembers.

(Supported by NSFC:30300398)