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MODELED MICROGRAVITY ALTERS INTEGRIN FUNCTION DURING OSTEOBLASTOGENESIS OF HUMAN MESENCHYMAL STEM CELLS.  V.E. Meyers¹, M. Zayzafoon¹, S.R. Gonda², W.E. Gathings³, J.M. McDonald¹.  ¹Dept of Pathology, Univ of Alabama, Birmingham, ²Cellular Biotechnology Program, NASA JSC, and ³CMDS, Univ of Alabama, Huntsville.

   Reduced bone mineral density during spaceflight is primarily attributed to decreased bone formation.  Reduced numbers of osteoblasts may contribute to this phenomenon.  We have previously demonstrated reduced osteoblastic differentiation of human mesenchymal stem cells (hMSC) in modeled microgravity (MMG).  Disruption of integrin-mediated signaling in MMG provides one potential mechanism for decreased differentiation.  Here, we characterize the effects of MMG on integrin expression and function during osteoblastogenesis of hMSC. 
   hMSC were seeded onto polystyrene microcarrier beads, and cell/bead aggregates formed for one week in DMEM containing 10% FBS.  Aggregates were then transferred to a rotary cell culture system, and osteoblastogenesis was induced immediately prior to initiation of MMG. 
   ₂ and ₁ integrin protein levels are increased 4-fold following 7 days MMG despite no change in gene expression for either subunit, suggesting altered protein degradation.  However, activation of integrin signaling through FAK is reduced 4-fold.  Because integrin signaling is required for hMSC differentiation, it is likely that this dysfunction contributes to the reduction in functional osteoblasts and the resulting decline in bone mineral density experienced during spaceflight.   (Support by the AL Space Grant Consortium and the Consortium for Materials Development in Space)