Identification of mechano-sensitive pathways in intervertebral disc cells

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Intervertebral discs form the soft connective tissue joints located along the length of the spine - required for spinal stabilization, load bearing, and movement. The major function of the intervertebral disc is to act as a shock absorber during mechanical loading. It is composed of distinct yet interdependent tissues including the central nucleus pulposus, which is highly hydrated and provides turgor to withstand compressive loading, and the outer annulus fibrosus which contains the nucleus pulposus and provides resistance to tensile strain. Although daily mechanical loading provides necessary feedback to cells of the disc to maintain the tissue's integrity, excessive loading contributes to disc degeneration by activating a cascade of non-reversible changes in disc cells that ultimately lead to an inability of the disc to fulfill its physiological function. The responses of specific disc cells to mechanical loading are therefore essential to maintaining a functional disc tissue. The effects of different types of mechanical loading (resulting from normal movement vs. exposure to vibration) on the distinct cell types of the disc are poorly understood, as are the cellular pathways that regulate these responses. ******The objective of these studies is to characterize the effects of mechanical loading on specific cell types of the disc, and explore which signaling pathways mediate the cellular response. We will use a genetically engineered mouse model that uses fluorescent cell markers to distinguish nucleus pulposus cells from annulus fibrosus cells. Cells grown in the lab will be subjected to mechanical loading in the form of either cyclic strain (physiological loading) or vibration (to model exposure to heavy machinery or vibration platforms) and the response of these cell types will be quantified through a series of experiments. These studies will give us a better fundamental understanding of how different cell types of the intervertebral disc respond to mechanical loading, information that is key to understanding how the disc maintains its structural integrity. Deciphering the pathways that control intervertebral disc mechanobiology will facilitate the development of tissue engineering strategies to recreate disc formation in vitro. *****