Cell mechanics and mechanobiology in the intervertebral disc

Study Design. A review is presented on current knowledge of the micromechanical factors in the intervertebral disc, their role in modifying cell biology, and changes with degeneration. Objectives. To identify current knowledge, knowledge gaps, and areas for future research in micromechanics of the intervertebral disc. Summary of Background Data. Mechanical factors play important roles in the initiation and progression of intervertebral disc degeneration. Evidence suggests that substantial biologic remodeling occurs in the intervertebral disc in response to mechanical stimuli that may play a critical role in determining the fate of a degenerating intervertebral disc. Information is needed on the precise mechanical stimuli that these cells experience and the mechanisms that govern their responses. Methods. A review is presented of cell morphology, cell mechanics, and the internal strains and other mechanical factors predicted to occur at the cell level. A review of intervertebral disc cell responses to well-controlled physical stimuli is also presented with a focus on in vitro studies of explants and isolated cells. Results. Important differences in cell morphology, mechanics, micromechanical factors, and mechanobiology are noted to occur between cells of the nucleus pulposus and anulus fibrosus. Changes in these features with degeneration are critically understudied, particularly degeneration-associated changes in cell morphology, cell mechanics, and altered physiology with mechanical loading. Conclusions. Information on the mechanisms that govern cell responses to mechanical stimuli in the intervertebral disc are just emerging. Studies must address determination of the factors that control micromechanical stimuli, but also mechanisms by which mechanics may interact with genetic factors to regulate expression and remodeling of extracellular matrix molecules, cytokines and mediators of pain and inflammation in degenerating tissue.