Microgravity Induction of TRAIL Expression in Preosteoclast Cells Enhances Osteoclast Differentiation

作者：Sambandam Yuvaraj; Baird Kelsey L; Stroebel Maxwell; Kowal Emily; Balasubramanian Sundaravadivel; Reddy Sakamuri V

来源：Scientific Reports, 2016, 6(1): 25143.

DOI：10.1038/srep25143

Evidence indicates that astronauts experience significant bone loss in space. We previously showed that simulated microgravity (mu Xg) using the NASA developed rotary cell culture system (RCCS) enhanced bone resorbing osteoclast (OCL) differentiation. However, the mechanism by which mu Xg increases OCL formation is unclear. RANK/RANKL signaling pathway is critical for OCL differentiation. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been shown to increase osteoclastogenesis. We hypothesize that TRAIL may play an important role in mu Xg enhanced OCL differentiation. In this study, we identified by RT profiler PCR array screening that mu Xg induces high levels of TRAIL expression in murine preosteoclast cells in the absence of RANKL stimulation compared to ground based (Xg) cultures. We further identified that mu Xg elevated the adaptor protein TRAF-6 and fusion genes OCSTAMP and DC-STAMP expression in preosteoclast cells. Interestingly, neutralizing antibody against TRAIL significantly reduced mu Xg induced OCL formation. We further identified that over-expression of pTRAIL in RAW 264.7 cells enhanced OCL differentiation. These results indicate that TRAIL signaling plays an important role in the mu Xg increased OCL differentiation. Therefore, inhibition of TRAIL expression could be an effective countermeasure for mu Xg induced bone loss.

• 出版日期2016-5-4