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Hypergravity reduces F-actin accumulation in osteoclasts, with attenuated bone resorption
Natsuhiro Takahashi1,2,3, Akihiko Fujita1,2,4, Yuki Azetsu1,2
1Department of Pharmacology, Graduate School of Dentistry, Showa Medical University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.
Plos One
|June 16, 2026
Summary
Astronauts experience bone loss due to microgravity. This study shows that osteoclasts, bone-resorbing cells, are sensitive to altered gravity, with hypergravity rapidly impairing their function and reducing bone resorption.
Area of Science:
- Skeletal Biology
- Cellular Mechanobiology
- Spaceflight Physiology
Background:
- Spaceflight induces bone loss, highlighting skeletal homeostasis sensitivity to gravity.
- Osteoclasts (bone-resorbing cells) may sense and respond to mechanical forces, including gravity.
Purpose of the Study:
- To investigate osteoclast sensitivity to gravity-generated mechanical loading.
- To elucidate the cellular mechanisms by which osteoclasts respond to hypergravity.
Main Methods:
- Osteoclasts derived from mouse bone marrow were exposed to hypergravity (3G, 5G, 30G) using centrifuge systems.
- Assessed cytoskeletal organization (F-actin, tubulin, vinculin) and resorptive function (TRAP staining, dentin pit assays).
- Performed quantitative phosphoproteomic analysis after 5G hypergravity exposure.
Main Results:
- Hypergravity rapidly compromised F-actin ring integrity and promoted nuclear repositioning.
- Structural changes correlated with attenuated bone resorption pit formation.
- Phosphoproteomic analysis revealed coordinated, gravity-dependent phosphorylation changes in key cellular pathways.
Conclusions:
- Osteoclasts are sensitive to mechanical loading from gravity.
- Hypergravity rapidly alters osteoclast cytoskeleton and signaling networks, reducing bone resorption.
- Findings offer mechanistic insights into skeletal adaptation during spaceflight and altered loading conditions.
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