2005 Fiscal Year Final Research Report Summary
THE ROLE OF NITRIC OXIDE, MATRIX METALLOPTOTEINASE AND TUMOR NECROTIZING FACTOR-α DURING THE PROCESS OF INTERVERTEBRAL DISC DEGENERATION AND REGENERATION
| Project/Area Number |
15591569
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | TOYAMA UNIVERSITY, UNIVERSITY HOSPITAL (2005)
Toyama Medical and Pharmaceutical University (2003-2004) |
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Principal Investigator |
ISHIHARA Hirokazu TOYAMA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISTANT PROFESSOR, 附属病院, 講師 (30242499)
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| Co-Investigator(Kenkyū-buntansha) |
OSADA Ryusuke TOYAMA UNIVERSITY, UNIVERSITY HOSPITAL, INSTRUCTOR, 附属病院, 助手 (40293310)
KAWAGUCHI Yoshiharu TOYAMA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISTANT PROFESSOR, 附属病院, 講師 (00262527)
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| Project Period (FY) |
2003 – 2005
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| Keywords | INTERVERETBRAL DISC DGENERATION / NITRIC OXIDE (NO) / MATRIX METALLOPROTEINASE / TUMOR NECROTIZING FACTOR |
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| Research Abstract |
The intervertebral disc degeneration is the major cause of disc dysfunction and low back pain. Many factors are known to influence intervertebral disc degeneration. The role of nitric oxide (NO), matrix metalloproteinase (MMP), and tumor necrotizing factor-α(TNF-α) in a variety of physiological processes of the intervertebral disc metabolism became apparent. We have clarified that the role of NO,MMP and TNF-α in disc metabolism and the effects of i-NOS inhibitor, MMP inhibitor and TNF-α inhibitor that control these production to prevent experimental rabbit disc degeneration model.
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.
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