| Autor: |
Snuggs JW; Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield, S1 1WB, UK., Tessier S; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Bunning RAB; Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield, S1 1WB, UK., Shapiro IM; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA., Risbud MV; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA., Le Maitre CL; Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield, S1 1WB, UK. C.Lemaitre@shu.ac.uk. |
| Abstrakt: |
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 TonEBP Δ/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. |
