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Cited by 31Bone Metabolism and DiseasesSpaceflight effects on biologyBone health and osteoporosis research

Microgravity induction of TRAIL expression in preosteoclast cells enhances osteoclast differentiation

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Sambandam, Yuvaraj, Baird, Kelsey L., Stroebel, Maxwell, Kowal, Emily, Balasubramanian, Sundaravadivel, Reddy, Sakamuri V.·2016·Scientific Reports
DOI 10.1038/srep25143PMC PMC4855152
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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.

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  • Expression of TRAIL, TRAF-6, and fusion genes OC-STAMP and DC-STAMP were upregulated in simulated microgravity in RAW 264.7 osteoclast precursors.

    “the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAF-6, and the fusion genes OC-STAMP and DC-STAMP were upregulated in simulated microgravity”

    From Osteoclasts and Microgravity (2020) · cites this paper as [68]

    The Results section on TRAIL expression reports upregulation in RAW 264.7 cells under simulated microgravity. The Results section on TRAF6 and fusion genes reports increased TRAF6, OC-STAMP, and DC-STAMP in mouse bone-marrow-derived preosteoclast cells, not specifically in RAW 264.7 cells. The claimed cell type is therefore supported for TRAIL but not for all four markers; page numbers were not available in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Sambandam, Y., Baird, K. L., Stroebel, M., Kowal, E., Balasubramanian, S., & Reddy, S. V.
Affiliations
Medical University of South Carolina (US)
Corresponding author
Reddy, Sakamuri V.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-05-04
Volume
6
Issue
1
Pages
25143-25143
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep25143
PMC
PMC4855152
OpenAlex
W2346271441
Cited by
31
References
4
Citations by year
2026: 3 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 9 · 2019: 7 · 2018: 4 · 2017: 2
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Medical University of South Carolina
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
microgravity, TRAIL, osteoclastogenesis, simulated microgravity, RANK/RANKL signaling, TRAF6, RAW 264.7 macrophages
MeSH terms
RAW 264.7 Cells, Animals, Cell Differentiation, Macrophages, Osteoclasts, Weightlessness, Transcriptional Activation, Polymerase Chain Reaction, Gene Expression Profiling, Microarray Analysis, Mice, TNF-Related Apoptosis-Inducing Ligand, RANK Ligand

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