Impact of simulated microgravity on human bone stem cells: New hints for space medicine

• Simulated microgravity activates stress response in bone mesenchymal stem cells.
• It induces the expression of several osteogenic markers apart from collagen1A1.
• Only the addition of an osteogenic cocktail leads to the deposition of calcium deposits.
• Simulated microgravity does not alter cell response to osteogenic stimuli.

Bone loss is a well known early event in astronauts and represents one of the major obstacle to space exploration. While an imbalance between osteoblast and osteoclast activity has been described, less is known about the behavior of bone mesenchymal stem cells in microgravity.We simulated microgravity using the Random Positioning Machine and found that mesenchymal stem cells respond to gravitational unloading by upregulating HSP60, HSP70, cyclooxygenase 2 and superoxyde dismutase 2. Such an adaptive response might be involved in inducing the overexpression of some osteogenic transcripts, even though the threshold to induce the formation of bone crystal is not achieved. Indeed, only the addition of an osteogenic cocktail activates the full differentiation process both in simulated microgravity and under static 1G-conditions.We conclude that simulated microgravity alone reprograms bone mesenchymal stem cells towards an osteogenic phenotype which results in complete differentiation only after exposure to a specific stimulus.