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 (classificati on, structure, substrate specificity and regulation) and to report pre vious studies of intervertebral discs. Summary of Background Data. Deg eneration of the intervertebral disc, a probable prerequisite to disc herniation, is a complex phenomenon, and its physiopathologic course r emains unclear. Matrix metalloproteinases probably play an important r ole but have received sparse attention in the literature. Methods. A s ystematic review of studies reporting a role of matrix metalloproteina ses in intervertebral disc degeneration. Results. In several studies, investigators have reported the presence of proteolytic enzymes from d isc culture systems and disc tissue extracts in degenerated human inte rvertebral discs, especially collagenase-1 (MMP-1) and stromelysin-l ( MMP-3). The matrix metalloproteinases are regulated by specific inhibi tors (tissue inhibitors of metalloproteinases, or TIMPS), cytokines (i nterleukin-l), and growth factors. Conclusions. This field of applicat ion is of particular interest because conventional treatments are disa ppointing in chronic low back pain. Clinical trials with specific inhi bitors of metalloproteinases are beginning in osteoarthritis.