TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc

SNUGGS, J. W., TESSIER, S., BUNNING, R. A. B., SHAPIRO, I. M., RISBUD, M. V. and LE MAITRE, Christine (2021). TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc. Scientific Reports, 11 (1), p. 3164.

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Open Access URL: https://www.nature.com/articles/s41598-021-81838-9 (Published version)
Link to published version:: https://doi.org/10.1038/s41598-021-81838-9
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    Abstract

    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.

    Item Type: Article
    Additional Information: ** From Springer Nature via Jisc Publications Router ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2045-2322 **Article IDs: publisher-id: s41598-021-81838-9; manuscript: 81838 **History: collection 12-2021; published 04-02-2021; online 04-02-2021; registration 13-01-2021; accepted 22-12-2020; submitted 14-08-2020
    Uncontrolled Keywords: Article, /631/80/304, /631/80, /631/337, /692/699/1670, article
    Identification Number: https://doi.org/10.1038/s41598-021-81838-9
    Page Range: p. 3164
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 09 Feb 2021 16:45
    Last Modified: 09 Feb 2021 16:45
    URI: http://shura.shu.ac.uk/id/eprint/28119

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