Matrix metalloproteinases: The clue to intervertebral disc degeneration?

Study Design. A review of the current literature on the role of matrix metalloproteinases in intervertebral disc degeneration. Objective. To detail the characteristics of matrix metalloproteinases (classification, structure, substrate specificity and regulation) and to report previous studies of intervertebral discs. Summary of Background Data. Degeneration of the intervertebral disc, a probable prerequisite to disc herniation, is a complex phenomenon, and its physiopathologic course remains unclear. Matrix metalloproteinases probably play an important role but have received sparse attention in the literature. Methods. A systematic review of studies reporting a role of matrix metalloproteinases in intervertebral disc degeneration. Results. In several studies, investigators have reported the presence of proteolytic enzymes from disc culture systems and disc tissue extracts in degenerated human intervertebral discs, especially collagenase-1 (MMP-1) and stromelysin-l (MMP-3). The matrix metalloproteinases are regulated by specific inhibitors (tissue inhibitors of metalloproteinases, or TIMPS), cytokines (interleukin-l), and growth factors. Conclusions. This field of application is of particular interest because conventional treatments are disappointing in chronic low back pain. Clinical trials with specific inhibitors of metalloproteinases are beginning in osteoarthritis.