Intervertebral disc plasticity in response to mechanical and biological perturbations

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Musculoskeletal tissues are constantly exposed to various types of stimuli and must respond adequately through remodelling to maintain homeostasis. The long-term goal of my research program is to advance our understanding of how the spine responds to mechanical and biological stimuli and how this ultimately affects biomechanics. Proposed experiments aim to investigate the effect of both mechanical and specifically inflammatory stimuli on the biomechanical properties at both the cellular and whole intervertebral disc level in the spine. It is anticipated that an interdependent relationship exists where either type of stimulant will perturb both biomechanical and biological equilibrium in the spine, thereby altering tissue structure (through remodelling) and function (mechanical integrity). Cells extracted from rat intervertebral discs will be embedded in collagen scaffolds which will then be exposed to mechanical and/or inflammatory stimulation. Following exposure, changes to the mechanical properties of the collagen scaffold (and therefore evidence of remodelling) as well as expression of tissue remodelling genes will be examined. Similarly, at the tissue level, whole discs will be exposed to similar stimuli and biomechanical properties of the intact discs will be quantified in order to discern remodelling in response to the stimulation. Last, exploratory experiments are aimed at uncovering the mechanistic pathways responsible for changes in disc biomechanics in response to both mechanical and inflammatory stimulation; this will be done by manipulating these pathways via receptor inhibition or altered regulation of tissue remodelling genes. This research will therefore provide a new understanding of the important pathways and processes involved in altering the mechanical properties of the intervertebral disc. Currently, minimal research is focused on the combination of these attributes making the proposed work novel in furthering our understanding of intervertebral disc function. Findings from this body of work also have the potential to assist in our understanding of disc pathologies, a prevalent issue among Canadian and significant source of disability worldwide.