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AB0018 Intervetebral disc herniation: involvement of metalloproteinases
  1. L Grange1,
  2. P Gaudin1,
  3. JJ Favre2,
  4. M Peoc’h3,
  5. R Juvin1,
  6. X Phelip1,
  7. JP Chirossel2,
  8. F Morel4
  1. 1Departement of Rheumatology
  2. 2Departement of Neurosurgery
  3. 3Departement of Pathology, Chu, Albert Michallon, Grenoble Universitary Teaching Hospital, Grenoble, France
  4. 4Grepi JE. EA 2019 MENRT (Groupe de Recherche Et D?Etude Du Processus Inflammatoire)

Abstract

Background Disc degeneration and physiopathology of disc herniation involves enzymatic processes mainly matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase-1 (TIMP-1) and cytokines (IL-1b, TNF-a).

Objectives This study focuses on metalloproteinases secretion and expression by disc chondrocytes isolated from herniated and not herniated zone.

Methods Eleven discs after discectomy are enzymatically digested, chondrocytes from both zones, herniated and not herniated, are cultured in alginate beads for 10 days in classical conditions. Analysis of MMP-2,-3,-7,-9,-13 and TIMP-1 by ELISA, zymography, RT-PCR and nested PCR are conducted with an immunochemical study on tissu fragments.

Results - proteic level: (ELISA, zymography):

?presence of elevated levels of MMP-3, TIMP-1 in the non herniated part

?absence of MMP-13, MMP-9, pro MMP-7 in both parts

-Transcriptional level (RT, PCR, nested PCR):

?expression of MMP-2, -3, TIMP-1 in both zones, weak expression of MMP-9 by nested PCR without difference between the two zones.

?absence or weak expression of MMP-13, -7.

Conclusion There is an heterogeneous expression of MMP -2, -3, -9 and TIMP-1 by disc herniated and non herniated chrondocytes. The matrix metalloproteinases are probably involved early in the disc degeneration, the herniation could be the final result of matrix/cells interactions.

The secretion of TIMP-1 and MMP-3 in the herniated zone may be related discal fibrosis included into the disc cicatrization.

References

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  2. Matsui Y, Maeda M, Nakagami W, Iwata H. Theinvolvement ofmatrixmetalloproteinases in inflammation in lumbar disc herniation. Spine 1998;23:863–9

  3. Crean JKG, Roberts S, Jaffray DC, Eisenstein SM, Duance VC. Matrix metalloproteinases in the human intervertebral disc. Role in disc degeneration and scoliosis. Spine 1997;22: 2877–84

  4. Haro H, Crawford HC, Fingleton B, et al. Matrisian. Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc résorption. J Clin Invest. 2000;105(2):133–41

  5. Poiraudeau S, Monteiro I, Anract P, Blanchard O, Revel M, Corvol MT. Phenotic characteristic of rabbit inter vertebral disccells. Spine 1999;24:837–44

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