Microarray profile of gene expression during osteoclast differentiation in modelled microgravity
Abstract
Microgravity (µXg) leads to a 10-15% loss of bone mass in astronauts during space flight. Osteoclast (OCL) is the multinucleated bone-resorbing cell. In this study, we used the NASA developed ground-based rotating wall vessel bioreactor (RWV), rotary cell culture system (RCCS) to simulate µXg conditions and demonstrated a significant increase (2-fold) in osteoclastogenesis compared to normal gravity control (Xg). Gene expression profiling of RAW 264.7 OCL progenitor cells in modelled µXg by Agilent microarray analysis revealed significantly increased expression of critical molecules such as cytokines/growth factors, proteases and signalling proteins, which play an important role in enhanced OCL differentiation/function. Transcription factors such as c-Jun, MITF and CREB implicated in OCL differentiation are upregulated; however no significant change in the levels of NFATc1 expression in preosteoclast cells subjected to modelled µXg. We also identified high-level expression of calcium-binding protein, S100A8 (calcium-binding protein molecule A8/calgranulin A) in preosteoclast cells under µXg. Furthermore, modelled µXg stimulated RAW 264.7 cells showed elevated cytosolic calcium (Ca(2+)) levels/oscillations compared to Xg cells. siRNA knock-down of S100A8 expression in RAW 264.7 cells resulted in a significant decrease in modelled µXg stimulated OCL differentiation. We also identified elevated levels of phospho-CREB in preosteoclast cells subjected to modelled µXg compared to X…
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Conditions of microgravity and simulated microgravity decrease osteoblastogenesis and osteoblast secretion of OPG.
“decrease osteoblastogenesis and osteoblast secretion of OPG”
From Osteoclasts and Microgravity (2020) · cites this paper as [66]
Conditions of microgravity and simulated microgravity decrease the mineral content and cortical and trabecular microstructures of bone.
“conditions of microgravity and simulated microgravity decrease the mineral content and cortical and trabecular microstructures of bone”
From Osteoclasts and Microgravity (2020) · cites this paper as [66]
Simulated microgravity upregulated production/expression of factors involved in osteoclastogenesis, including cytokines, growth factors, proteases, signaling proteins, and transcription factors c-Jun, MITF, and CREB, compared to ground controls.
“upregulated the production/expression of factors involved in osteoclastogenesis, including cytokines, growth factors, proteases, signaling proteins, and transcription factors c-Jun, MITF, and CREB as compared to ground controls [66]”
From Osteoclasts and Microgravity (2020) · cites this paper as [66]
Conditions of microgravity and simulated microgravity increase osteoclast secretion of sclerostin.
“increase osteoclast secretion of sclerostin”
From Osteoclasts and Microgravity (2020) · cites this paper as [66]
Simulated microgravity increased osteoclastogenesis by twofold in RAW 264.7 osteoclast progenitor cells compared to ground controls.
“Sambandam and associates found that simulated microgravity increased osteoclastogenesis by twofold”
From Osteoclasts and Microgravity (2020) · cites this paper as [66]
Conditions of microgravity and simulated microgravity increase osteoclast differentiation, fusion, and expression of regulatory and osteoclast-specific genes.
“increase osteoclast differentiation, fusion, and expression of regulatory and osteoclast-specific genes”
From Osteoclasts and Microgravity (2020) · cites this paper as [66]
Cites
Transforming Growth Factor-β1 to the Bone
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“TGF-b has multiple functions in the bone environment and is required for early OCL progenitor commitment and suppress OCL apoptosis [Janssens et al., 2005; Gingery et al., 2008].”
BackgroundReduction in proximal femoral strength due to long-duration spaceflight
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Microgravity control of autophagy modulates osteoclastogenesis
Sambandam, Y., Townsend, M. T., Pierce, J. J., Lipman, C. M., Haque, A., Bateman, T. A., & Reddy, S. V. (2014) · Bone · doi:10.1016/j.bone.2014.01.004 · Cited by 93 · see citing works
Self-citationSmith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
- Authors
- Sambandam, Y., Blanchard, J. J., Daughtridge, G., Kolb, R. J., Shanmugarajan, S., Pandruvada, S. N. M., Bateman, T. A., & Reddy, S. V.
- Affiliations
- Medical University of South Carolina (US)
- Clemson University (US)
- Corresponding author
- Reddy, Sakamuri V.
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2010-11-29
- Volume
- 111
- Issue
- 5
- Pages
- 1179-1187
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W1992401482
- Cited by
- 62
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- osteoclastogenesis, microgravity, simulated microgravity, rotating wall vessel bioreactor, RAW 264.7 macrophages, S100A8, calcium-binding proteins, intracellular calcium, CREB phosphorylation, c-Jun, MITF, NFATc1, gene expression profiling, bone resorption, spaceflight bone loss
- MeSH terms
- Animals, Bone Resorption, Cell Differentiation, Cell Line, Macrophages, Models, Biological, Osteoclasts, Space Flight, Weightlessness, Astronauts, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Fractures, Bone, Mice
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