Cells from Degenerative Intervertebral Discs Demonstrate Unfavorable Responses to Mechanical and Inflammatory Stimuli

Abstract

Mechanical forces and inflammatory signaling influence intervertebral disc matrix homeostasis. We hypothesized that annulus fibrosus cells from degenerative discs would have altered responses to mechanical and inflammatory stimuli compared with cells isolated from normal discs. Annulus fibrosus cells were isolated from New Zealand White rabbits with normal and magnetic resonance imaging-confirmed degenerative discs created by annular stab. Cells were cultured with and without inflammatory and mechanical stimuli (tensile strain). After 4 or 24 hrs, the mRNA expression of inflammatory, catabolic, and anabolic genes was measured by reverse transcription polymerase chain reaction. Baseline gene expression differences were noted between cells from normal and degenerative discs. Degenerative cells demonstrated a more proinflammatory response profile to inflammatory and mechanical stimuli and loss of the beneficial effects of mechanical signaling. Decreased expression of catabolic and anabolic genes was observed in degenerative cells under conditions of inflammatory and mechanical stimuli. These data demonstrate that degenerative cells have a decreased capacity to respond positively to beneficial levels of mechanical strain and demonstrate an exaggerated response to an inflammatory stimulus. This may, in part, help to explain differential responses to motion-based therapies in patients with intervertebral disc degeneration.