Simulated microgravity upregulates gene expression of the skeletal regulator Core binding Factor α1/Runx2 in Medaka fish larvae in vivo

Long-term space flight results in significant bone loss in humans. However, it remains to be shown how microgravity affects the expression of genes involved in modeling and remodeling of bone material in vivo. For these analyses, animal models are instrumental to study alterations at the molecular and cellular level. Although it is not known at present, whether fish loose bone in microgravity, they show many experimental advantages to approach these questions in vivo. Here, we report for the first time that living Medaka larvae can be used in hypergravitation and clinorotation experiments to study the effect of altered gravity on gene expression in a whole-animal situation. Living Medaka larvae at 1 day post-hatching were exposed to hypergravity and simulated microgravity for 24 hours (h) and the level of mRNA expression of skeletal regulators was determined by real-time RT-PCR. No effect of altered gravity was observed on the expression of osteoprotegerin (opg) genes that regulate osteoclast formation in humans. However, clinorotation resulted in a significant increase of expression of core binding factor α1 (cbfa1/runx2), a crucial regulator of osteoblast formation. Exposure to hypergravitation for 24 h on the other hand had no effect on cbfa1/runx2 expression. This shows that cbfa1/runx2 responds to reduced gravity by expression level changes in vivo. Furthermore, it demonstrates that Medaka provides a valuable experimental model to study molecular mechanisms for compensating microgravity induced bone loss.