Altered expression of mRNAs implicated in osteogenesis under conditions of simulated microgravity is regulated by CD200:CD200R

Mouse calvarial cells grown under simulated microgravity conditions (neutral buoyancy) show preferential differentiation towards the osteoclast lineage, as defined by surrogate mRNAs, bone nodule growth and TRAP⁺ cells, when compared with cells cultured under normal gravity conditions. This effect was suppressed in cultures which contained the immunoregulatory molecule CD200, and conversely enhanced by anti-CD200 mAb. Concomitant increases occur in expression of inflammatory cytokines, and their mRNAs, under simulated microgravity conditions. Again cultures containing exogenous CD200 showed suppressed cytokine and cytokine mRNA expression. Further alterations in osteoclastogenesis were seen using cells isolated from cytokine-receptor knockout mice. We conclude that, as assessed by altered expression of mRNAs associated with osteoblast differentiation, CD200:CD200R interactions play an important regulatory role in the enhanced osteoclastogenesis seen under simulated microgravity conditions, with changes in cytokine expression further modulating this effect.