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IGF-I SIGNALING IN RAT OSTEOBLAST DURING SPACE FLIGHT.    Y. Kumei¹, H. Akiyama², M. Hirano², H. Nakamura³, S. Morita⁴, K. Ohya¹, K. Shinomiya³ and  H. Shimokawa¹.  ¹Dept of Hard Tissue Engineering, and ³Orthopaedic and Spinal Surgery,  ⁴Division of Rehabilitation Medicine, Graduate School of Tokyo Medical and Dental Univ.,  Tokyo, Japan. ²Toray Research Center, Kamakura, Japan.

We examined microgravity effects on the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), and insulin receptor substrate-1 (IRS-1), a signaling molecule of IGF-I, in rat osteoblasts.  Quadruplicate culture of cells were treated on board with 1a, 25 (OH)2D3 for 22 hrs, and fixed by guanidine isothiocyanate solution on the 5th day of space shuttle mission.  The entire sequence of the procedure was repeated and fixed on the 6th day of the mission.  After return to the Earth, the mRNA levels of IGF-IR, IGF-I and IRS-1 were examined by the quantitative reverse transcription-polymerase chain reaction.  The mRNA levels of IGF-IR in the flight cultures were significantly increased to 173 % (p<0.05) and 186% (p<0.01) of the ground controls on the 5th and 6th days of the mission, respectively.  However, the gene transcripts of IGF-I and IRS-1 were not at all detected in the flight cultures, which was clearly contrasted to the ground control cultures.  All the data were reproduced by the repeated flight experiments.  Microgravity increased the IGF-IR mRNA levels but decreased the IGF-I and IRS-1 mRNA levels. Disturbance in IGF-I signaling in osteoblasts might be involved in reduced bone formation in microgravity.

(Supported by National Space Development Agency and Institute of Space and Astronautical Science, Japan)