Degeneration of the intervertebral disc has been implicated in chronic low back pain. Type II collagen and proteoglycan (predominantly aggrecan) content is crucial to proper disc function, particularly in the nucleus pulposus. In degeneration, synthesis of matrix molecules changes, leading to an increase in the synthesis of collagens type I and III and a decreased production of aggrecan. Linked to this is an increased expression of matrix-degrading molecules including MMPs (matrix metalloproteinases) and the aggrecanases, ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) 1, 4, 5, 9 and 15, all of which are produced by native disc cells. Importantly, we have found that there is a net increase in these molecules, over their natural inhibitors [TIMP-1 (tissue inhibitor of metalloproteinases-1), 2 and 3], suggesting a deregulation of the normal homoeostatic mechanism. Growth factors and cytokines [particularly TNFα (tumour necrosis factor α) and IL-1 (interleukin 1)] have been implicated in the regulation of this catabolic process. Our work has shown that in degenerate discs there is an increase in IL-1, but no corresponding increase in the inhibitor IL-1 receptor antagonist. Furthermore, treatment of human disc cells with IL-1 leads to a decrease in matrix gene expression and increased MMP and ADAMTS expression. Inhibition of IL-1 would therefore be an important therapeutic target for preventing/reversing disc degeneration.
Skip Nav Destination
Article navigation
August 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
July 20 2007
Matrix synthesis and degradation in human intervertebral disc degeneration
C.L. Le Maitre;
C.L. Le Maitre
*Tissue Injury and Repair Group, School of Medicine, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, U.K.
Search for other works by this author on:
A. Pockert;
A. Pockert
*Tissue Injury and Repair Group, School of Medicine, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, U.K.
Search for other works by this author on:
D.J. Buttle;
D.J. Buttle
†Academic Unit of Molecular Medicine, School of Medicine and Biomedical Sciences, E-Floor, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, U.K.
Search for other works by this author on:
A.J. Freemont;
A.J. Freemont
*Tissue Injury and Repair Group, School of Medicine, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, U.K.
Search for other works by this author on:
J.A. Hoyland
J.A. Hoyland
1
*Tissue Injury and Repair Group, School of Medicine, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, U.K.
1To whom correspondence should be addressed (email judith.hoyland@manchester.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 14 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 652–655.
Article history
Received:
March 14 2007
Citation
C.L. Le Maitre, A. Pockert, D.J. Buttle, A.J. Freemont, J.A. Hoyland; Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem Soc Trans 1 August 2007; 35 (4): 652–655. doi: https://doi.org/10.1042/BST0350652
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.