ASGSB 2003 Annual Meeting Abstracts
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
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
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
Space Grant Consortium and the Consortium for Materials Development in Space)
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