Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc - PubMed

Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc

Christine Lyn Le Maitre et al. J Pathol. 2004 Sep.

Abstract

The histological and biochemical changes that occur in the extracellular matrix of the intervertebral disc (IVD) during ageing and degeneration have been investigated extensively. However, the mechanisms behind these changes are not fully understood. A number of studies have suggested the involvement of matrix metalloproteinases (MMPs) and ADAMTS in IVD degeneration, but few have localized the site of production of these enzymes to the cells of the degenerate disc. This study uses immunohistochemical techniques to localize and quantify the production of degrading enzymes (MMPs 1, 3, and 13, and ADAMTS 4) and their inhibitors (TIMPS 1, 2, and 3) within non-degenerate and degenerate discs of varying severity of degeneration. In all discs investigated, the cells that produced the enzymes and their inhibitors were the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus (AF), with little immunopositivity in the outer AF. Non-degenerate discs showed low numbers of cells expressing the degradative enzymes MMP 1 and ADAMTS 4, suggesting a role for these enzymes in normal homeostasis. No MMP 3 or MMP 13 immunopositivity was observed in non-degenerate discs. In degenerate discs, the number of cells immunopositive for MMPs 1, 3, 13 and ADAMTS 4 increased with the severity of degeneration. This increase in degrading enzymes was also accompanied by increases in the number of cells immunopositive for TIMPs 1 and 2 but not TIMP 3. This study highlights that although the expression of a number of MMPs increases with degeneration, this is accompanied by an increase in their inhibitors. However, the increase in the number of cells immunoreactive for ADAMTS 4 with increasing degeneration was not paralleled by a rise in its inhibitor TIMP 3. This finding indicates that the aggrecanases, rather then the MMPs, are a possible therapeutic target for the inhibition of disc degeneration.

Similar articles

• Aggrecanases and aggrecanase-generated fragments in the human intervertebral disc at early and advanced stages of disc degeneration.

  Patel KP, Sandy JD, Akeda K, Miyamoto K, Chujo T, An HS, Masuda K. Patel KP, et al. Spine (Phila Pa 1976). 2007 Nov 1;32(23):2596-603. doi: 10.1097/BRS.0b013e318158cb85. Spine (Phila Pa 1976). 2007. PMID: 17978660

• Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration.

  Yurube T, Takada T, Suzuki T, Kakutani K, Maeno K, Doita M, Kurosaka M, Nishida K. Yurube T, et al. Arthritis Res Ther. 2012 Mar 6;14(2):R51. doi: 10.1186/ar3764. Arthritis Res Ther. 2012. PMID: 22394620 Free PMC article.

• 2002 SSE Award Competition in Basic Science: expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption.

  Weiler C, Nerlich AG, Zipperer J, Bachmeier BE, Boos N. Weiler C, et al. Eur Spine J. 2002 Aug;11(4):308-20. doi: 10.1007/s00586-002-0472-0. Epub 2002 Jul 9. Eur Spine J. 2002. PMID: 12193991 Free PMC article.

• Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration.

  Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA, Kang JD. Vo NV, et al. Spine J. 2013 Mar;13(3):331-41. doi: 10.1016/j.spinee.2012.02.027. Epub 2013 Jan 29. Spine J. 2013. PMID: 23369495 Free PMC article. Review.

• Matrix synthesis and degradation in human intervertebral disc degeneration.

  Le Maitre CL, Pockert A, Buttle DJ, Freemont AJ, Hoyland JA. Le Maitre CL, et al. Biochem Soc Trans. 2007 Aug;35(Pt 4):652-5. doi: 10.1042/BST0350652. Biochem Soc Trans. 2007. PMID: 17635113 Review.

Cited by

• Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell.

  Yu C, Li D, Wang C, Xia K, Wang J, Zhou X, Ying L, Shu J, Huang X, Xu H, Han B, Chen Q, Li F, Tang J, Liang C, Slater N. Yu C, et al. Bioact Mater. 2021 Mar 23;6(10):3568-3579. doi: 10.1016/j.bioactmat.2021.03.018. eCollection 2021 Oct. Bioact Mater. 2021. PMID: 33842742 Free PMC article.

• Inflammation in intervertebral disc degeneration and regeneration.

  Molinos M, Almeida CR, Caldeira J, Cunha C, Gonçalves RM, Barbosa MA. Molinos M, et al. J R Soc Interface. 2015 Mar 6;12(104):20141191. doi: 10.1098/rsif.2014.1191. J R Soc Interface. 2015. PMID: 25673296 Free PMC article. Review.

• Detrimental role for human high temperature requirement serine protease A1 (HTRA1) in the pathogenesis of intervertebral disc (IVD) degeneration.

  Tiaden AN, Klawitter M, Lux V, Mirsaidi A, Bahrenberg G, Glanz S, Quero L, Liebscher T, Wuertz K, Ehrmann M, Richards PJ. Tiaden AN, et al. J Biol Chem. 2012 Jun 15;287(25):21335-45. doi: 10.1074/jbc.M112.341032. Epub 2012 May 3. J Biol Chem. 2012. PMID: 22556410 Free PMC article. Clinical Trial.

• Matrix metalloproteinase 28, a novel matrix metalloproteinase, is constitutively expressed in human intervertebral disc tissue and is present in matrix of more degenerated discs.

  Gruber HE, Ingram JA, Hoelscher GL, Zinchenko N, Norton HJ, Hanley EN Jr. Gruber HE, et al. Arthritis Res Ther. 2009;11(6):R184. doi: 10.1186/ar2876. Epub 2009 Dec 9. Arthritis Res Ther. 2009. PMID: 20003223 Free PMC article.

• Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and pain-related behavior.

  Wawrose RA, Couch BK, Dombrowski M, Chen SR, Oyekan A, Dong Q, Wang D, Zhou C, Chen J, Modali K, Johnson M, Sedor-Schiffhauer Z, Hitchens TK, Jin T, Bell KM, Lee JY, Sowa GA, Vo NV. Wawrose RA, et al. JOR Spine. 2022 May 13;5(2):e1202. doi: 10.1002/jsp2.1202. eCollection 2022 Jun. JOR Spine. 2022. PMID: 35783914 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal