Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion
Abstract
Exposure to microgravity has been associated with several physiological changes in astronauts, including an osteoporosis-like loss in bone mass. Despite many in vivo and in vitro studies in both microgravity and simulated microgravity conditions, the mechanism for bone loss is still not clear. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to assess bone cell responses. In this work, we conduct a unique investigation of the effects of microgravity on bone-producing osteoblasts and, in parallel, on bone-resorbing osteoclasts. An increase in total number of discrete resorption pits is observed in osteoclasts that experienced microgravity versus ground controls. We further show that osteoblasts exposed to 5 days of microgravity have shorter and wavier microtubules (MTs), smaller and fewer focal adhesions, and thinner cortical actin and stress fibers. Space-flown osteoblasts present extended cell shapes as well as significantly more disrupted and often fragmented or condensed nuclei. The absence of gravitational forces therefore causes both an increase in bone resorption by osteoclasts, and a decrease in osteoblast cellular integrity. The observed effects on both major bone cell types likely accelerate bone loss in microgravity environments, and additionally offer a potential explanation to the development of disuse osteoporosis on Earth.
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Microgravity increased the resorptive activity of osteoclasts compared to ground controls, based on analysis of approximately 16,000 resorptive pits on Osteologic slides.
“In contrast, on analyzing approximately 16,000 resorptive pits on Osteologic slides, they found that microgravity increased the resorptive activity of osteoclasts when compared to that of ground controls, underscoring the resilience of these cells to the effects of zero gravity [54].”
From Osteoclasts and Microgravity (2020) · cites this paper as [54]
Spaceflight osteoblasts had shorter and curvier microtubules, a reduced number and size of focal adhesins, and more condensed and fragmented nuclei compared to ground controls.
“The authors found that spaceflight osteoblasts had shorter and curvier microtubules, a reduced number and size of focal adhesins, and more condensed and fragmented nuclei when compared to ground controls, findings in keeping with other reports on the adverse effects of microgravity osteoblast cytoskeleton integrity.”
From Osteoclasts and Microgravity (2020) · cites this paper as [54]
Osteoclasts maintain their ability to resorb bone in microgravity, in contrast to osteoblasts and osteocytes, which are adversely affected by microgravity.
“In stark contrast to the devastating effects of microgravity on osteoblasts, whose cytoskeletons may implode do to the failure of microtubules and actin filaments [54,55], and osteocytes, which undergo apoptosis as early as three days into space flight [56], osteoclasts maintain their ability to resorb bone in microgravity.”
From Osteoclasts and Microgravity (2020) · cites this paper as [54]
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Blaber, E. A., Dvorochkin, N., Lee, C., Alwood, J. S., Yousuf, R., Pianetta, P., Globus, R. K., Burns, B. P., & Almeida, E. A. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061372 · Cited by 196 · see citing works
Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
- Authors
- Nabavi, N., Khandani, A., Camirand, A., & Harrison, R. E.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Jewish General Hospital (CA)
- Corresponding author
- Harrison, Rene E.
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 49
- Issue
- 5
- Pages
- 965-974
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W2081263377
- Cited by
- 174
- References
- 0
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 12 · 2023: 9 · 2022: 20 · 2021: 7 · 2020: 19 · 2019: 12 · 2018: 13 · 2017: 5 · 2016: 9 · 2015: 15 · 2014: 14 · 2013: 8 · 2012: 4
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- 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
- microgravity, osteoclasts, osteoblasts, bone resorption, bone loss, disuse osteoporosis, cytoskeleton, focal adhesions, microtubules, stress fibers, cell adhesion, resorption pits, nuclear fragmentation, simulated microgravity, spaceflight
- MeSH terms
- Animals, Bone Resorption, Cell Adhesion, Cells, Cultured, Cytoskeleton, Microscopy, Electron, Scanning, Osteoblasts, Osteoclasts, Weightlessness, Cell Proliferation, Mice
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