Immunohistochemical Study of Matrix Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinase-1 in Human Intervertebral Discs


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Abstract

Study Design.Immunohistologic staining of human intervertebral discs collected at the time of surgery (100 intervertebral discs from 80 patients) and 10 discs collected from 7 cadavers within 12 hours of death was performed using antimatrix metalloproteinase-3 monoclonal antibody and antitissue inhibitor of metalloproteinase-1 monoclonal antibody.Objectives.To examine the relationship between matrix destruction and staining for matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in intervertebral disc degeneration.Summary of Background Data.Matrix metalloproteinase-3, which decomposes aggregating proteoglycans, has attracted research attention as a substance contributing to matrix destruction in the articular cartilage and intervertebral disc. However, except for a few in vitro studies, the relationship between matrix destruction of the intervertebral disc and matrix metalloproteinase-3 has been little studied.Methods.Immunohistologic staining was performed to examine the relationship between matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in the intervertebral disc, and the relationship of these two agents to magnetic resonance imaging, radiographic, and surgical findings.Results.Those cases testing positive for matrix metalloproteinase-3 and negative for tissue inhibitor of metalloproteinase-1 accounted for most of the surgical specimens. The matrix metalloproteinase-3-positive cell ratio was significantly correlated with the magnetic resonance imaging grade of intervertebral disc degeneration, and the matrix metalloproteinase-3-positive cell ratio observed in prolapsed lumbar intervertebral discs was significantly higher than that in nonprolapsed discs. In cervical intervertebral discs, the matrix metalloproteinase-3-positive cell ratio and staining of cartilaginous endplate were correlated with the size of osteophyte formation.Conclusions.These findings suggested that intervertebral disc degeneration is caused by disturbance in the equilibrium of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1, and that matrix metalloproteinase-3 contributes to degeneration of the cartilaginous endplate.

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