Advertisement

Rheumatology International

, Volume 1, Issue 2, pp 69–72 | Cite as

The effects of dexamethasone in vitro on the production of collagenase and inhibitor by synovial and cartilage explants from the joints of rabbits with a proliferative arthritis

  • G. J. Cambray
  • G. Murphy
  • J. J. Reynolds
Originals

Summary

Using a rabbit model arthritis we have investigated the ability of dexamethasone to alter the production of collagenase and the specific metallo-proteinase inhibitor TIMP by explants of synovium and cartilage in vitro. The patterns of collagenase and TIMP production by untreated explants from arthritic joint tissues in culture were similar to those described previously [1, 2]. Dexamethasone dramatically altered the patterns of production of collagenase and TIMP. At a dose of 10 nM, or above, the patterns of production by treated synovium resembled those of normal rabbit synovium: collagenase production was suppressed and TIMP increased compared with untreated arthritic synovium. The levels of latent collagenase in cartilage also fell with increasing doses of dexamethasone and TIMP levels were higher, although normal levels were not reached.

These experiments have been conducted as a prelude to testing the effects of various anti-rheumatic drugs in vivo, and attempting to correlate changes in clinical parameters with the subsequent production of collagenase and TIMP in vitro. The data are discussed in relation to the therapeutic use of corticosteroids and to their mode of action on joint tissues.

Key words

Dexamethasone Collagenase TIMP Synovium Cartilage Rabbits 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cambray GJ, Murphy G, Page-Thomas DP, Reynolds JJ (1981) The production in culture of metallo-proteinases and an inhibitor by joint tissues from normal rabbits, and from rabbits with a model arthritis. I. Synovium. Rheumatol Int 1:11–16Google Scholar
  2. 2.
    Murphy G, Cambray GJ, Virani N, Page-Thomas DP, Reynolds JJ (1981) The production in culture of metalloproteinases and an inhibitor by joint tissues from normal rabbits, and from rabbits with a model arthritis. II. Articular cartilage. Rheumatol Int 1:17–20Google Scholar
  3. 3.
    Page-Thomas DP (1977) Aspects of synovial biodegradation. In: Bayer-Symposium VI. Experimental models of chronic inflammatory diseases. Springer, Berlin Heidelberg New York. pp 353–365Google Scholar
  4. 4.
    Cawston TE, Galloway WA, Mercer E, Murphy G, Reynolds JJ (1981) Purification of rabbit bone inhibitor of collagenase. Biochem J 195:159–165Google Scholar
  5. 5.
    Snedecor GW, Cochran WG (1973) Statistical methods, 6th ed. Iowa State University Press, AmesGoogle Scholar
  6. 6.
    Sellers A, Meikle MC, Reynolds JJ (1980) Collagenase and collagenase inhibitor levels following changes in bone resorption in vitro. Calcif Tissue Int 31:35–43Google Scholar
  7. 7.
    Dayer J-M, Krane SM, Russell RGG, Robinson DR (1976) Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. Proc Natl Acad Sci USA 73:945–949Google Scholar
  8. 8.
    Brinckerhoff CE, McMillan RM, Dayer J-M, Harris ED (1980) Inhibition by retinoic acid of collagenase production in rheumatoid synovial cells. N Engl J Med 303:432–436Google Scholar
  9. 9.
    Reynolds JJ (1980) The effects of hydrocortisone on the production of collagenase and inhibitor by connective tissues in vitro. In: Richards RJ, Rajan KT (eds) Tissue culture in medical research. Pergamon Press, Oxford New York, pp 11–18Google Scholar
  10. 10.
    Ciosek CP, Harrity TW (1980) Cartilage-associated collagenolytic activity in rabbits with antigen-induced chronic synovitis. J Lab Clin Med 96:460–469Google Scholar
  11. 11.
    Panagides J, Landes MJ, Sloboda AE (1980) Destruction of articular cartilage by arthritic synovium in vitro: mechanism of breakdown and effect of indomethacin and prednisolone. Agents Actions 10:22–30Google Scholar
  12. 12.
    Phillips NC, Page-Thomas DP, Knight CG, Dingle JT (1979) Liposome-incorporated corticosteroids. II. Therapeutic activity in experimental arthritis. Ann Rheum Dis 38:553–557Google Scholar
  13. 13.
    Blacow NW, Wade A (eds) (1972) Corticosteroids. In: Martindale: The extra pharmacopoeia, 26th ed. The Pharmaceutical Press, London, pp 488–530Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • G. J. Cambray
    • 1
  • G. Murphy
    • 1
  • J. J. Reynolds
    • 1
  1. 1.Cell Physiology DepartmentStrangeways Research LaboratoryCambridgeUK

Personalised recommendations