Irisin prevents microgravity-induced impairment of osteoblast differentiation in vitro during the space flight CRS-14 mission

Understanding molecular mechanisms responsible for bone cells unbalance in microgravity would allow the development of better countermeasures for astronauts, and eventually advancing terrestrial osteoporosis treatments. We conduct a unique investigation by using a controlled 3D in vitro cell model to mimic the bone microenvironment in microgravity aboard the SpaceX Dragon cargo ferry to the ISS. Osteoblasts (OBs), osteoclasts (OCs), and endothelial cells (ECs), seeded on Skelite discs, were cultured w/ or w/o rec-Irisin and exposed to 14 days of microgravity in the eOSTEO hardware. Gene expression analysis was assessed, and results were compared to ground controls treated within identical payloads. Our results show that the microgravity-induced downregulation of mRNA levels of genes encoding for OB key transcription factors (Atf4 −75%, P <.01; RunX2 −87%, P <.001, Osterix −95%, P <.05 vs ground) and proteins (Collagen I −84%, P <.05; Osteoprotegerin −94%, P <.05) were prevented by irisin. Despite it was not effective in preventing Trap and Cathepsin K mRNA increase, irisin induced a 2.8-fold increase of Osteoprotegerin (P <.05) that might act for reducing osteoclastogenesis in microgravity. Our results provide evidence that irisin supports OB differentiation and activity in microgravity and it might represent a countermeasure to prevent bone loss in astronauts.