Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 in intervertebral disc degeneration and disc herniation

Abstract

We have evaluated the correlation between disc herniation or degeneration and the levels of matrix metalloproteinase-3 (MMP-3) or tissue inhibitor of metalloproteinases-1 (TIMP-1). The lumbar discs obtained from 22 autopsied cadavers and 21 patients with lumbar disc herniation were examined. Immunohistochemical study: The number of MMP-3-producing and TIMP-1-producing cells increased as disc herniation or degeneration progressed. Zymography: Activated type MMP-3 was observed in the normal and herniated intervertebral disc excluding the intervertebral disc with protrusion-type herniation. RT-PCR: The MMP-3 gene was expressed in all groups. However, the expression of the TIMP-1 gene was weak in the normal group as well as in the protrusion type disc herniation. Determination of tissue and serum levels of MMP-3 and TIMP-1 was increased as disc degeneration or herniation progressed. There were positive correlations between the number of MMP-3-producing or TIMP-1-producing cells in the intervertebral disc and the tissue or serum levels of MMP-3 and TIMP-1. These results suggested that MMP-3 and TIMP-1 were closely related to the progression of disc degeneration or herniation. The results also suggested that MMP-3 and TIMP-1 exhibited similar kinetics. Moreover, the serum levels of MMP-3 and TIMP-1 reflected the progression of disc degeneration and herniation.