IMMUNOHISTOCHEMICAL STUDY OF MATRIX METALLOPROTEINASE-3 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN HUMAN INTERVERTEBRAL DISCS

Study Design. Immunohistologic staining of human invertebral discs col lected at the time of surgery (100 intervertebral discs from 80 patien ts) and 10 discs collected from 7 cadavers within 12 hours of death wa s performed using antimatrix metalloproteinase-3 monoclonal antibody a nd antitissue inhibitor of metalloproteinase-1 monoclonal antibody. Ob jectives. To examine the relationship between maxtrix destruction and staining for matrix metalloproteinase-3 and tissue inhibitor of metall oproteinase-1 in intervertebral disc degeneration. Summary of Backgrou nd Data. Matrix metalloproteinase-3, which decomposes aggregating prot eoglycans, has attracted research attention as a substance contributin g to matrix destruction in the articular cartilage and intervertebral disc. However, except for a few in vitro studies, the relationship bet ween matrix destruction of the intervertebral disc and matrix metallop roteinase-3 has been little studied. Methods. Immunohistologic stainin g was performed to examine the relationship between matrix metalloprot einase-3 and tissue inhibitor of metalloproteinase-1 in the interverte bral disc, and the relationship of these two agents to magnetic resona nce imaging, radiographic, and surgical findings. Results. Those cases testing positive for matrix metalloproteinase-3 and negative for tiss ue inhibitor of metalloproteinase-1 accounted for most of the surgical specimens. The matrix metalloproteinase-3-positive cell ratio was sig nificantly correlated with the magnetic resonance imaging grade of int ervertebral disc degeneration, and the matrix metalloproteinase-3-posi tive cell ratio observed in prolapsed lumbar intervertebral discs was significantly higher than that in nonprolapsed discs. In cervical inte rvertebral discs, the matrix metalloproteinase-3-positive cell ratio a nd staining of cartilaginous endplate were correlated with the size of osteophyte formation. Conclusions. These findings suggested that inte rvertebral disc degeneration is caused by disturbance in the equilibri um of matrix metalloproteinase-3 and tissue inhibitor of metalloprotei nase-1, and that matrix metalloproteinase-3 contributes to degeneratio n of the cartilaginous endplate.