Osteoblast and osteoclast differentiation in modeled microgravity.

Prolonged microgravity experienced by astronauts is asso- ciated with a decrease in bone mineral density. To investigate the ef- fect of microgravity on differentiation of osteoclasts and osteoblasts, we used a NASA-recommended, ground-based, microgravity-simulating system, the Rotary Cell Culture System (RCCS). Using the RCCS, we demonstrated that modeled microgravity (MMG) inhibited osteoblasto- genesis and increased adipocyte differentiation in human mesenchymal stem cells incubated under osteogenic conditions. This transformation involves reduced RhoA activity and cofilin phosphorylation, disruption of F-actin stress fibers, and decreased integrin signaling through focal adhesion kinase. We have used the system to show that MMG also stim- ulates osteoclastogenesis. These systems provide the opportunity to de- velop pharmacological agents that will stimulate osteoblastogenesis and inhibit osteoclastogenesis.