Atp6v1h Deficiency Blocks Bone Loss in Simulated Microgravity Mice through the Fos-Jun-Src-Integrin Pathway Article Swipe
Zanyan Zhao
,
Xiangpu Wang
,
Yu Ma
,
Xiaohong Duan
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/ijms25010637
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/ijms25010637
The microgravity conditions in outer space are widely acknowledged to induce significant bone loss. Recent studies have implicated the close relationship between Atp6v1h gene and bone loss. Despite this, the role of Atp6v1h in bone remodeling and its molecular mechanisms in microgravity have not been fully elucidated. To address this, we used a mouse tail suspension model to simulate microgravity. We categorized both wild-type and Atp6v1h knockout (Atp6v1h+/-) mice into two groups: regular feeding and tail-suspension feeding, ensuring uniform feeding conditions across all cohorts. Analysis via micro-CT scanning, hematoxylin-eosin staining, and tartrate-resistant acid phosphatase assays indicated that wild-type mice underwent bone loss under simulated microgravity. Atp6v1h+/- mice exhibited bone loss due to Atp6v1h deficiency but did not present aggravated bone loss under the same simulated microgravity. Transcriptomic sequencing revealed the upregulation of genes, such as Fos, Src, Jun, and various integrin subunits in the context of simulated microgravity and Atp6v1h knockout. Real-time quantitative polymerase chain reaction (RT-qPCR) further validated the modulation of downstream osteoclast-related genes in response to interactions with ATP6V1H overexpression cell lines. Co-immunoprecipitation indicated potential interactions between ATP6V1H and integrin beta 1, beta 3, beta 5, alpha 2b, and alpha 5. Our results indicate that Atp6v1h level influences bone loss in simulated microgravity by modulating the Fos-Jun-Src-Integrin pathway, which, in turn, affects osteoclast activity and bone resorption, with implications for osteoporosis. Therefore, modulating Atp6v1h expression could mitigate bone loss in microgravity conditions. This study elucidates the molecular mechanism of Atp6v1h’s role in osteoporosis and positions it as a potential therapeutic target against environmental bone loss. These findings open new possibilities for the treatment of multifactorial osteoporosis.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms25010637
- https://www.mdpi.com/1422-0067/25/1/637/pdf?version=1704336540
- OA Status
- gold
- Cited By
- 3
- References
- 37
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390586955
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Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4390586955Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms25010637Digital Object Identifier
- Title
-
Atp6v1h Deficiency Blocks Bone Loss in Simulated Microgravity Mice through the Fos-Jun-Src-Integrin PathwayWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-04Full publication date if available
- Authors
-
Zanyan Zhao, Xiangpu Wang, Yu Ma, Xiaohong DuanList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms25010637Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/25/1/637/pdf?version=1704336540Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/25/1/637/pdf?version=1704336540Direct OA link when available
- Concepts
-
Osteoclast, Bone resorption, Downregulation and upregulation, Knockout mouse, Gene knockout, Cell biology, Context (archaeology), Integrin, Chemistry, Bone remodeling, Biology, Endocrinology, Cell, Receptor, Gene, Biochemistry, PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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3Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2024: 2Per-year citation counts (last 5 years)
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37Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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