• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Nov 2005; 64(Suppl 4): iv44–iv47.
PMCID: PMC1766921

What are the roles of metalloproteinases in cartilage and bone damage?

Abstract

A role for metalloproteinases in the pathological destruction in diseases such as rheumatoid arthritis and osteoarthritis, and the irreversible nature of the ensuing cartilage and bone damage, have been the focus of much investigation for several decades. This has led to the development of broad spectrum metalloproteinase inhibitors as potential therapeutics. More recently it has been appreciated that several families of zinc dependent proteinases play significant and varied roles in the biology of the resident cells in these tissues, orchestrating development, remodelling, and subsequent pathological processes. They also play key roles in the activity of inflammatory cells. The task of elucidating the precise role of individual metalloproteinases is therefore a burgeoning necessity for the final design of metalloproteinase inhibitors if they are to be employed as therapeutic agents.

Full Text

The Full Text of this article is available as a PDF (111K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Fosang AJ, Stanton H, Little CB, Atley LM. Neoepitopes as biomarkers of cartilage catabolism. Inflamm Res. 2003 Jun;52(7):277–282. [PubMed]
  • Poole A Robin, Nelson Fred, Dahlberg Leif, Tchetina Elena, Kobayashi Masahiko, Yasuda Tadashi, Laverty Sheila, Squires Ginette, Kojima Toshihisa, Wu William, et al. Proteolysis of the collagen fibril in osteoarthritis. Biochem Soc Symp. 2003;(70):115–123. [PubMed]
  • Kevorkian Lara, Young David A, Darrah Clare, Donell Simon T, Shepstone Lee, Porter Sarah, Brockbank Sarah M V, Edwards Dylan R, Parker Andrew E, Clark Ian M. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004 Jan;50(1):131–141. [PubMed]
  • Nagase Hideaki, Kashiwagi Masahide. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther. 2003;5(2):94–103. [PMC free article] [PubMed]
  • Mengshol John A, Mix Kimberlee S, Brinckerhoff Constance E. Matrix metalloproteinases as therapeutic targets in arthritic diseases: bull's-eye or missing the mark? Arthritis Rheum. 2002 Jan;46(1):13–20. [PubMed]
  • Coussens Lisa M, Fingleton Barbara, Matrisian Lynn M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002 Mar 29;295(5564):2387–2392. [PubMed]
  • Rao B Govinda. Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. Curr Pharm Des. 2005;11(3):295–322. [PubMed]
  • Puente Xose S, Sánchez Luis M, Overall Christopher M, López-Otín Carlos. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet. 2003 Jul;4(7):544–558. [PubMed]
  • Overall Christopher Mark, López-Otín Carlos. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657–672. [PubMed]
  • Clark Ian M, Parker Andrew E. Metalloproteinases: their role in arthritis and potential as therapeutic targets. Expert Opin Ther Targets. 2003 Feb;7(1):19–34. [PubMed]
  • Patwari P, Gao G, Lee JH, Grodzinsky AJ, Sandy JD. Analysis of ADAMTS4 and MT4-MMP indicates that both are involved in aggrecanolysis in interleukin-1-treated bovine cartilage. Osteoarthritis Cartilage. 2005 Apr;13(4):269–277. [PMC free article] [PubMed]
  • Dickinson Sally C, Vankemmelbeke Mireille N, Buttle David J, Rosenberg Krisztina, Heinegård Dick, Hollander Anthony P. Cleavage of cartilage oligomeric matrix protein (thrombospondin-5) by matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs. Matrix Biol. 2003 May;22(3):267–278. [PubMed]
  • Flannery CR, Little CB, Caterson B, Hughes CE. Effects of culture conditions and exposure to catabolic stimulators (IL-1 and retinoic acid) on the expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) by articular cartilage chondrocytes. Matrix Biol. 1999 Jun;18(3):225–237. [PubMed]
  • Andersen Thomas L, del Carmen Ovejero Maria, Kirkegaard Tove, Lenhard Thomas, Foged Niels T, Delaissé Jean-Marie. A scrutiny of matrix metalloproteinases in osteoclasts: evidence for heterogeneity and for the presence of MMPs synthesized by other cells. Bone. 2004 Nov;35(5):1107–1119. [PubMed]
  • Verrier S, Hogan A, McKie N, Horton M. ADAM gene expression and regulation during human osteoclast formation. Bone. 2004 Jul;35(1):34–46. [PubMed]
  • Mott Joni D, Werb Zena. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol. 2004 Oct;16(5):558–564. [PMC free article] [PubMed]
  • Mohammed FF, Smookler DS, Khokha R. Metalloproteinases, inflammation, and rheumatoid arthritis. Ann Rheum Dis. 2003 Nov;62 (Suppl 2):ii43–ii47. [PMC free article] [PubMed]
  • Garnero Patrick, Mazières Bernard, Guéguen Alice, Abbal Michel, Berdah Laurent, Lequesne Michel, Nguyen Minh, Salles Jean-Pierre, Vignon Eric, Dougados Maxime. Cross-sectional association of 10 molecular markers of bone, cartilage, and synovium with disease activity and radiological joint damage in patients with hip osteoarthritis: the ECHODIAH cohort. J Rheumatol. 2005 Apr;32(4):697–703. [PubMed]
  • Baker Andrew H, Kritz Angelika, Work Lorraine M, Nicklin Stuart A. Cell-selective viral gene delivery vectors for the vasculature. Exp Physiol. 2005 Jan;90(1):27–31. [PubMed]
  • Lee Meng-Huee, Rapti Magdalini, Murphy Gillian. Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme. J Biol Chem. 2005 Apr 22;280(16):15967–15975. [PubMed]
  • van der Laan WH, Quax PHA, Seemayer CA, Huisman LGM, Pieterman EJ, Grimbergen JM, Verheijen JH, Breedveld FC, Gay RE, Gay S, et al. Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3. Gene Ther. 2003 Feb;10(3):234–242. [PubMed]
  • Vincenti MP, Brinckerhoff CE. The potential of signal transduction inhibitors for the treatment of arthritis: Is it all just JNK? J Clin Invest. 2001 Jul;108(2):181–183. [PMC free article] [PubMed]
  • Mix Kimberlee S, Sporn Michael B, Brinckerhoff Constance E, Eyre David, Schurman David J. Novel inhibitors of matrix metalloproteinase gene expression as potential therapies for arthritis. Clin Orthop Relat Res. 2004 Oct;(427 Suppl):S129–S137. [PubMed]
  • Voils Stacy A, Evans Martin E, Lane Matthew T, Schosser Robert H, Rapp Robert P. Use of macrolides and tetracyclines for chronic inflammatory diseases. Ann Pharmacother. 2005 Jan;39(1):86–94. [PubMed]

Figures and Tables

Figure 1
 Three metzincin families, matrix metalloproteinases (MMPs), disintegrin metalloproteinases (ADAMs), and disintegrin metalloproteinases with thrombospondin repeats (ADAM TSs) have been identified as having roles in the biology and pathology of ...
Figure 2
 Modification of the metalloproteinase binding ridge of tissue inhibitors of metalloproteinases (TIMPs) to generate potent inhibitors of TACE. Based on any of the four TIMP basic scaffolds a tight binding inhibitor of the disintegrin metalloproteinase ...

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...