Unlocking the mechanisms of mechanotransduction in degenerative disc disease
Degeneration of the intervertebral disc has enormous economic consequences due to its association with low back pain. Although it is well known that biomechanical factors play an integral role in the development of painful degenerative disc disease, the mechanisms by which disc cells convert mechanical signals into biochemical responses are to date almost completely unknown. As a consequence, it is still unclear how mechanical signals can lead to both, disc homeostasis and disc degeneration, and why cells in degenerating discs respond differently to mechanical, osmotic and inflammatory signals than cells in healthy discs. Ultimately, the link between mechanical signals, degeneration, inflammation and pain is simply not understood in the disc, despite the clinical relevance and the tremendous therapeutic potential.
In order to unlock the mechanisms of mechanotransduction in degenerative disc disease, this project will focus on an intriguing drug target that has recently emerged: the transient receptor potential (TRP) channels. TRPs are ubiquitous and relevant in the sensing of osmotic, mechanical and inflammatory stress and play an important role in multiple diseases. Using an interdisciplinary approach (engineering, biology, medicine, pharmacology) ranging from in vitro cell and tissue culture studies to in vivo knockout studies, this project will aim to identify the mechanisms of mechanotransduction that are involved in disc pathology. The ultimate goal of this project will be to to promote healthy ageing by therapeutically regulating TRP channels.