2021 Volume No 41 – pages 121-141
Title: Osmotic adaptation of nucleus pulposus cells: the role of aquaporin 1, aquaporin 4 and transient receptor potential vanilloid 4 |
Authors: JW Snuggs, RAD Bunning, CL Le Maitre |
Address: Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield S1 1WB, UK. |
E-mail: C.Lemaitre at shu.ac.uk |
Abstract: The microenvironment of the nucleus pulposus is hyperosmotic and fluctuates diurnally due to mechanical
loading. Changes in extracellular osmolality result in cell volume alterations, responsiveness to such changes
is essential for cellular homeostasis. Aquaporins allow movement of water across cell membranes and control
water permeability in response to osmotic gradients. Furthermore, transient receptor potential vanilloid 4 has
been shown to sense osmotic and mechanical stimuli resulting in changes to intracellular Ca2+. It has been
shown previously that aquaporin 1 and 4 expression decreases during disc degeneration. Here, the expression
of transient receptor potential vanilloid 4 by human nucleus pulposus cells during disc degeneration, and
the roles of aquaporin 1, 4 and transient receptor potential vanilloid 4 in regulating responses to osmotic
gradients was investigated. Transient receptor potential vanilloid 4 was expressed by the majority of human
nucleus pulposus cells and not affected by disc degeneration. Aquaporin 4 staining co-localised with primary
cilia. Nucleus pulposus cells modulated their rate of volume change, water permeability and Ca2+ influx in
response to extracellular osmolality. These responses were inhibited by chemical inhibition of aquaporin 4,
transient receptor potential vanilloid 4, and to a lesser extent aquaporin 1; suggesting that both aquaporins
and transient receptor potential vanilloid 4 play important roles in the fundamental adaptation of nucleus
pulposus cells to their osmotic environment. Co-localisation with primary cilia indicates these proteins may
function synergistically to achieve adaptation, which may be lost during disc degeneration, when aquaporin
1 and 4 expression is reduced. |
Key Words: Aquaporin, TRPV4, nucleus pulposus, osmotic adaptation, water permeability. |
Publication date: February 02th 2021 |
Article download: Pages
121-141 (PDF file) |
