title: Microgravity Induction of TRAIL Expression in Preosteoclast Cells Enhances Osteoclast Differentiation.
abstract: Evidence indicates that astronauts experience significant bone loss in space. We previously showed that simulated microgravity (μXg) using the NASA developed rotary cell culture system (RCCS) enhanced bone resorbing osteoclast (OCL) differentiation. However, the mechanism by which μXg 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 μXg enhanced OCL differentiation. In this study, we identified by RT profiler PCR array screening that μXg 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 μXg elevated the adaptor protein TRAF-6 and fusion genes OC-STAMP and DC-STAMP expression in preosteoclast cells. Interestingly, neutralizing antibody against TRAIL significantly reduced μXg 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 μXg increased OCL differentiation. Therefore, inhibition of TRAIL expression could be an effective countermeasure for μXg induced bone loss.
authors.affiliation: Darby Children's Research Institute, Charleston, SC, USA.
authors.forename: Yuvaraj
authors.initials: Y
authors.lastname: Sambandam
authors.affiliation: Darby Children's Research Institute, Charleston, SC, USA.
authors.forename: Kelsey L
authors.initials: KL
authors.lastname: Baird
authors.affiliation: Darby Children's Research Institute, Charleston, SC, USA.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Stroebel
authors.affiliation: Darby Children's Research Institute, Charleston, SC, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Kowal
authors.affiliation: Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Sundaravadivel
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Darby Children's Research Institute, Charleston, SC, USA.
authors.forename: Sakamuri V
authors.initials: SV
authors.lastname: Reddy
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D008264:Macrophages / Q000502:physiology; D051379:Mice; D046228:Microarray Analysis; D010010:Osteoclasts / Q000502:physiology*; D016133:Polymerase Chain Reaction; D053245:RANK Ligand / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D015533:Transcriptional Activation; D014893:Weightlessness
chemical_list: D053245:RANK Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; C505689:Tnfsf11 protein, mouse