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ALTERED GRAVITY INCREASES PGE2 PRODUCTION THROUGH ACTIVATION OF COX-2 mRNA EXPRESSION IN MOUSE OSTEOBLAST LIKE MC3T3-E1 CELLS.    A. Sato¹, M. Fujita¹, M. Kanematsu¹, M. Narato², H. Kumagai², S. Kamigaichi¹ and M. Takaoki¹. ¹Space Utilization Research Programme, National Space Development Agency of Japan, Tsukuba-shi, Ibaraki 305-8505, Japan, ²Advanced Engineering Services Co., Tsukuba-shi, Ibaraki 305-0032, Japan.

Prostaglandin E₂ (PGE₂) is a bone-resorbing and bone-forming substance produced by osteoblasts.  Altered gravity regulates bone remodeling.  The purpose of this study was to clarify effects of altered gravity on the PGE₂ production and cyclooxygenase (COX) mRNA expression in osteoblast-like MC3T3-E1 cells. The cells were exposed to simulated microgravity or hypergravity for 1.5, 3, 6, 12 and 24 h.  Their PEG₂ production and COX-1 and COX-2 mRNA expression were assessed. Results indicate that; 1) simulated microgravity obtained in a clinostat demonstrated 6- and 14- fold increase in PGE₂ level in culture media of cells after 3 and 6 h culture compared with those of cells in control (stationary culture); 2) COX-1 mRNA expression did not significantly change but COX-2 mRNA expression increased 3.5- and 1.5- fold after 1.5 and 3 h, then declined to 1/2-fold 24 h later in cells exposed to simulated microgravity; 3)  Hypergravity (5, 10 and 20g) induced the increase in PGE₂ level in culture media and in expression of COX-2 mRNA in cells; 4) Nabumetone (35-100μM), a COX-2 inhibitor completely blocked altered gravity-induced PGE₂ production of cells. These results indicate that both clinorotation and centrifugation could modify bone remodeling by COX-2 mRNA expression, suggesting altered gravity might be functioning as a mechanical stressor in cells.