THE ROLE OF NITRIC OXIDE, MATRIX METALLOPTOTEINASE AND TUMOR NECROTIZING FACTOR-α DURING THE PROCESS OF INTERVERTEBRAL DISC DEGENERATION AND REGENERATION

Radiographs revealed intervertebral disc space narrowing after 1 month after surgery. Histologically, the reduction of Safranin-O staining and production of annulus fibrosus tear during the degeneration process are apparent. The synthetic activities of proteoglycan and DNA were also decreased. MMP 1,3,9,12,13, and TIMP 1 and 2 were determined by sandwich enzyme immunoassay method. These enzymes were increased dramatically in the intervertebral disc degeneration process, and the degenerated rabbit intervertebral disc spontaneously produced NO and NO inhibited proteoglycan synthesis in the disc. We investigated the effect of i-NOS inhibitor (L-LMMA), MMP inhibitor and TNF-α inhibitor on the degenerated process of the disc. NO inhibitor inhibited the NO production and proteoglycan synthesis rate, but had no effect on MMP and TNF-α production. But, TNF-α inhibitor inhibited TNF-α and MMP production, and also inhibited degeneration process of the disc. From these results, it is important to inhibit TNF-α and MMP production to promote intervertebral disc regeneration.