Microgravity modulation of syncytin-A expression enhance osteoclast formation.

ABSTRACT

Microgravity (µXg) experienced by astronauts during space flights causes accelerated bone loss. However, the molecular basis of µXg induced bone loss in space is unclear. Osteoclast (OCL) is the primary bone-resorbing cell. We previously demonstrated that simulated µXg promotes OCL formation. In this study, we identified that µXg induces syncytin-A expression in RAW264.7 preosteoclast cells without RANKL stimulation. We further tested the effect of osteotropic factors such as CXCL5 and 1,25(OH)2 D3 to regulate the syncytin-A expression in preosteoclast cells subjected to µXg compared to ground based (Xg) cultures. CXCL5 (25 ng/mL) and 1,25(OH)2 D3 (10 ng/mL) increased syncytin-A expression under Xg conditions. However, µXg alone upregulates syncytin-A expression compared to Xg control preosteoclast cells. Confocal microscopy using Lyso-Tracker identified syncytin-A expression co-localized with lysosomes in preosteoclast cells. Acridine orange staining showed RANKL elevated autophagy activity in these cells. Further, siRNA suppression of syncytin-A significantly inhibits autophagy activity in RAW264.7 cells. In addition, knockdown of syncytin-A expression inhibits µXg increased OCL formation in mouse bone marrow cultures. Thus, our findings suggest that targeting syncytin-A expression may be an effective countermeasure to control bone loss under microgravity conditions.