Inflammation and Disc Degeneration

Intervertebral disc (IVD) degeneration in patients is associated with chronic elevated levels of multiple pro-inflammatory cytokines, indicative of the important roles that inflammatory mediators play in the degenerative etiology.  We have developed an animal model, using direct intradiscal stimulation of innate immunity in the IVD, to explore the role of inflammation in triggering degeneration.  We are studying novel inflammatory and injury mediators (HMGB1) and their signaling through  toll-like receptors in IVD cells.  We find that inflammatory insults alone, in the absence of traumatic injury, triggers degeneration of the IVD.  This is physiologically relevant because we have identified a chemical trigger and disease mechanism of degeneration that mimics the molecular profile of human disc degeneration and may be amenable to pharmacological treatments.  We are evaluatin

g pharmacological inhibitors of these pathways for the treatment of IVD degeneration.