TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc
Abstract The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonE...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-81838-9 |
| _version_ | 1818952342972661760 |
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| author | J. W. Snuggs S. Tessier R. A. B. Bunning I. M. Shapiro M. V. Risbud C. L. Le Maitre |
| author_facet | J. W. Snuggs S. Tessier R. A. B. Bunning I. M. Shapiro M. V. Risbud C. L. Le Maitre |
| author_sort | J. W. Snuggs |
| collection | DOAJ |
| description | Abstract The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic conditions mimicking the osmolality of the healthy IVD, which was abrogated by TonEBP knockdown. Furthermore, AQP1 and 5 immunopositivity was significantly reduced in TonEBPΔ/Δ E17.5 mice when compared with wildtype controls, indicating in vivo expression of AQP1 and 5 is controlled at least in part by TonEBP. This hyperosmotic regulation of AQP1 and 5 could help to explain the decreased AQP1 and 5 expression during degeneration, when the osmolality of the NP decreases. Together this data suggests that TonEBP-regulated osmo-adaptation may be disrupted during IVD degeneration when the expression of both AQPs is reduced. |
| first_indexed | 2024-12-20T09:48:52Z |
| format | Article |
| id | doaj.art-4138b596e4be471abac6b99852763239 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T09:48:52Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4138b596e4be471abac6b998527632392022-12-21T19:44:41ZengNature PortfolioScientific Reports2045-23222021-02-0111111210.1038/s41598-021-81838-9TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral discJ. W. Snuggs0S. Tessier1R. A. B. Bunning2I. M. Shapiro3M. V. Risbud4C. L. Le Maitre5Biomolecular Sciences Research Centre, Sheffield Hallam UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson UniversityBiomolecular Sciences Research Centre, Sheffield Hallam UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson UniversityBiomolecular Sciences Research Centre, Sheffield Hallam UniversityAbstract The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic conditions mimicking the osmolality of the healthy IVD, which was abrogated by TonEBP knockdown. Furthermore, AQP1 and 5 immunopositivity was significantly reduced in TonEBPΔ/Δ E17.5 mice when compared with wildtype controls, indicating in vivo expression of AQP1 and 5 is controlled at least in part by TonEBP. This hyperosmotic regulation of AQP1 and 5 could help to explain the decreased AQP1 and 5 expression during degeneration, when the osmolality of the NP decreases. Together this data suggests that TonEBP-regulated osmo-adaptation may be disrupted during IVD degeneration when the expression of both AQPs is reduced.https://doi.org/10.1038/s41598-021-81838-9 |
| spellingShingle | J. W. Snuggs S. Tessier R. A. B. Bunning I. M. Shapiro M. V. Risbud C. L. Le Maitre TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc Scientific Reports |
| title | TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc |
| title_full | TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc |
| title_fullStr | TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc |
| title_full_unstemmed | TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc |
| title_short | TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc |
| title_sort | tonebp regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc |
| url | https://doi.org/10.1038/s41598-021-81838-9 |
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