Atp6v1h Deficiency Blocks Bone Loss in Simulated Microgravity Mice through the Fos-Jun-Src-Integrin Pathway.
Zanyan Zhao1, Xiangpu Wang1, Yu Ma1
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
International Journal of Molecular Sciences
|January 11, 2024
Summary
The gene Atp6v1h influences bone loss in simulated microgravity by affecting osteoclast activity. Modulating Atp6v1h may prevent microgravity-induced bone loss and treat osteoporosis.
Area of Science:
- Biomedical Science
- Molecular Biology
- Space Medicine
Background:
- Microgravity causes significant bone loss, a critical concern for astronauts.
- The gene Atp6v1h is linked to bone loss, but its role in microgravity-induced bone remodeling is unclear.
Purpose of the Study:
- To investigate the role of Atp6v1h in microgravity-induced bone loss.
- To elucidate the molecular mechanisms by which Atp6v1h affects bone remodeling under simulated microgravity.
Main Methods:
- Utilized a mouse tail suspension model to simulate microgravity.
- Employed micro-CT, histology, gene expression analysis (RNA-seq, RT-qPCR), and co-immunoprecipitation.
Main Results:
- Simulated microgravity induced bone loss in wild-type mice.
- Atp6v1h knockout mice showed bone loss but no aggravation under simulated microgravity.
- Identified the Fos-Jun-Src-Integrin pathway as modulated by Atp6v1h in microgravity, affecting osteoclast activity.
Conclusions:
- Atp6v1h level impacts microgravity-induced bone loss by regulating osteoclast function via the Fos-Jun-Src-Integrin pathway.
- Atp6v1h is a potential therapeutic target for mitigating bone loss in microgravity and treating multifactorial osteoporosis.
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