The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation

Study Design. Surgically obtained herniated lumbar disc specimens were stained with hematoxylin-eosin or toluidine blue (for detection of proteoglycans) or were immunostained with monoclonal antibodies (CD68), antihuman interstitial collagenase (matrix metalloproteinase [MMP]-1) and antihuman stromelysin (MMP-3). Objective. To investigate the possible correlation of matrix metalloproteinase activity to granulation tissue formation and lumbar disc herniation, depending on the type of herniation. Summary of Background Data. Interstitial collagenase and stromelysin have been implicated in the degradation of the matrix of articular cartilage in rheumatoid arthritis, osteoarthritis and degenerated disc tissues. However, their role in the herniation of the intervertebral disc has received little study. Methods. Twenty-one specimens of lumbar disc herniation (classified as protrusions, subligamentous extrusions, transligamentous extrusions, and sequestrations) and four nonherniated discs were stained with hematoxylin-eosin or toluidine blue or were immunostained with monoclonal antibodies to CD20, CD45RO, and CD68, anti-MMP-1, and anti-MMP-3, using the avidin-biotin-peroxidase complex method. The amount of granulation tissue and results of staining were graded to examine differences in histology among the four herniation types. Results. In sequestration and transligamentous extrusion specimens, granulation tissue containing many CD68-positive macrophages was commonly observed. Most cells in granulation tissue, as well as chondrocytes, stained positively with anti-MMP-1 and anti-MMP-3 antibodies. Granulation tissue was less commonly observed in subligamentous extrusions and was absent from most protrusion specimens and all nonherniated specimens. B and T lymphocytes could not be demonstrated in granulation tissue. Conclusions. The increased staining of MMP-1 and MMP-3 associated with inflammatory cells of granulation tissue in herniated discs suggests a causal correlation of these proteinases to tissue degradation in herniation.