Synergistic effect of IL-4 and simulated microgravity on osteogenic differentiation of periosteal stem cells

In space, astronauts' cortical bone demonstrates a more stable maintenance of bone mass compared to the trabecular bone. In our previous research, enhanced periosteal bone formation, along with increased osteogenic differentiation capacity of periosteal stem cells (PSCs) under simulated microgravity (SMG) by clinostat was demonstrated. This phenomenon may contribute to the relative stability of astronauts' cortical bone under microgravity, whereas the underlying mechanism remains unclear. In this study, the contribution of Interleukin-4 (IL-4) and its synergistic effect with simulated microgravity to osteogenesis of PSCs were studied. The results showed that rats experiencing simulated weightlessness through tail suspension developed elevated IL-4 levels in the soleus muscle and periosteum, with serum IL-4 concentrations remaining unaltered. In vitro, primary PSCs were treated with recombinant IL-4, and the effects of IL-4 on the proliferation and differentiation of PSCs were investigated under simulated microgravity. It also demonstrated that simulated microgravity and IL-4 have a synergistic promoting effect on the osteogenic differentiation of PSCs. The findings of this study demonstrate that IL-4 and simulated microgravity exert a synergistic effect on the differentiation and osteogenesis of periosteal stem cells, potentially playing a beneficial role in the maintenance of cortical bone under microgravity conditions.