Abstract
The IVD is a highly hydrated, hyperosmolar tissue that allows the correct biomechanical function of the spine. When degenerated, water and ions are lost from the disc, especially within the central nucleus pulposus (NP), producing a hypoosmotic environment in which the resident cells can no longer function correctly, exacerbating the degenerative cascade. One potential way that IVD cells may adapt to their environment is through the expression and regulation of aquaporin (AQP) channels that control the movement of water in and out of cells. During human IVD degeneration AQP1 and 5 expression is decreased, highlighting AQPs may be of importance for the correct function of NP cells. The regulation of AQPs in NP cells by healthy and degenerate conditions, and the potential underlying molecular mechanisms, were investigated in both human and rat IVD cells. The gene and protein expression of AQP1 and AQP5 was upregulated by hyperosmotic conditions (425mOsm/kg H2O) in rat and human NP cells. Lentiviral knockdown of tonicity enhancer binding protein (TonEBP), a transcription factor responsible for maintaining the function of NP cells, resulted in the loss of AQP1 and 5 gene expression under hyperosmotic conditions. The maintenance of the IVD environment and adaptation of cells is vital for the function of the IVD. The regulation of AQPs by physiological conditions and TonEBP suggests a role for these water channels related to the adaptation of disc cells to their environment, which is dysregulated during degeneration.
