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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1993 Apr;52(4):292–299. doi: 10.1136/ard.52.4.292

Effect of tenidap on cartilage integrity in vitro.

J T Dingle 1, M R Leeming 1, J J Martindale 1
PMCID: PMC1005628  PMID: 8484696

Abstract

OBJECTIVES--The maintenance of articular cartilage integrity during long term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is of clinical importance. These experiments were set up to test the action of tenidap, naproxen, and diclofenac on bovine and porcine cartilage, matrix synthesis, and catabolism. METHODS--Short term organ culture techniques were used to determine the effect of interleukin 1 (IL-1) on synthesis and degradation, and the action of tenidap and the other drugs on these parameters. The retention of glycosaminoglycans (GAGs) and the synthesis of GAGs by incorporation of sulphur-35 labelled sulphate was used to determine the chondrocyte metabolic activity. RESULTS--The action of human recombinant interleukin 1 alpha (hrIL-1 alpha) in increasing catabolic activity and inhibiting synthetic activity of the animal cartilages was confirmed. Tenidap was shown to give substantial and significant protection against the catabolic effects of hrIL-1 alpha and, to a lesser degree, against the inhibition of matrix synthesis by the cytokine. Neither diclofenac nor naproxen in doses expected to occur in the synovial fluid showed this action. Tenidap also inhibited the GAG loss from cocultures and, to a moderate degree, reversed the inhibition of synthesis by synovial tissue. Tenidap also stimulated cartilage repair activity during recovery from IL-1 treatment. The optimum concentration of the action against IL-1 was between 5 and 10 micrograms/ml. Above this concentration tenidap itself showed some inhibitory action on GAG synthesis. CONCLUSIONS--Bearing in mind the problems in extrapolating from in vitro work on animal cartilages to humans, it seems possible that tenidap may be useful in decreasing the deleterious action of cytokines such as IL-1 on cartilage integrity during arthritic disease and in stimulating chondrocyte repair processes.

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Selected References

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  1. Bird T. A., Saklatvala J. Identification of a common class of high affinity receptors for both types of porcine interleukin-1 on connective tissue cells. Nature. 1986 Nov 20;324(6094):263–266. doi: 10.1038/324263a0. [DOI] [PubMed] [Google Scholar]
  2. Blackburn W. D., Jr, Heck L. W., Loose L. D., Eskra J. D., Carty T. J. Inhibition of 5-lipoxygenase product formation and polymorphonuclear cell degranulation by tenidap sodium in patients with rheumatoid arthritis. Arthritis Rheum. 1991 Feb;34(2):204–210. doi: 10.1002/art.1780340212. [DOI] [PubMed] [Google Scholar]
  3. Brandt K. D. Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am J Med. 1987 Nov 20;83(5A):29–34. doi: 10.1016/0002-9343(87)90848-5. [DOI] [PubMed] [Google Scholar]
  4. Dinarello C. A. Interleukin-1: amino acid sequences, multiple biological activities and comparison with tumor necrosis factor (cachectin). Year Immunol. 1986;2:68–89. [PubMed] [Google Scholar]
  5. Dingle J. T. Heberden oration 1978. Recent studies on the control of joint damage: the contribution of the Strangeways Research Laboratory. Ann Rheum Dis. 1979 Jun;38(3):201–214. doi: 10.1136/ard.38.3.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dingle J. T., Horsfield P., Fell H. B., Barratt M. E. Breakdown of proteoglycan and collagen induced in pig articular cartilage in organ culture. Ann Rheum Dis. 1975 Aug;34(4):303–311. doi: 10.1136/ard.34.4.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dingle J. T. The effect of synovial catabolin on cartilage synthetic activity. Connect Tissue Res. 1984;12(3-4):277–286. doi: 10.3109/03008208409013690. [DOI] [PubMed] [Google Scholar]
  8. Farndale R. W., Sayers C. A., Barrett A. J. A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res. 1982;9(4):247–248. doi: 10.3109/03008208209160269. [DOI] [PubMed] [Google Scholar]
  9. Fell H. B., Jubb R. W. The effect of synovial tissue on the breakdown of articular cartilage in organ culture. Arthritis Rheum. 1977 Sep-Oct;20(7):1359–1371. doi: 10.1002/art.1780200710. [DOI] [PubMed] [Google Scholar]
  10. Fowler P. D., Shadforth M. F., Crook P. R., John V. A. Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis. Eur J Clin Pharmacol. 1983;25(3):389–394. doi: 10.1007/BF01037953. [DOI] [PubMed] [Google Scholar]
  11. Herman J. H., Appel A. M., Khosla R. C., Hess E. V. In vitro effect of select nonsteroidal antiinflammatory drugs on the synthesis and activity of anabolic regulatory factors produced by osteoarthritic and rheumatoid synovial tissue. J Rheumatol. 1989 Jan;16(1):75–81. [PubMed] [Google Scholar]
  12. Hess E. V., Herman J. H. Cartilage metabolism and anti-inflammatory drugs in osteoarthritis. Am J Med. 1986 Nov 28;81(5B):36–43. [PubMed] [Google Scholar]
  13. Jalava S., Saarimaa H., Anttila M., Sundquist H. Naproxen concentrations in serum, synovial fluid, and synovium. Scand J Rheumatol. 1977;6(3):155–157. doi: 10.3109/03009747709095441. [DOI] [PubMed] [Google Scholar]
  14. Krane S. M., Dayer J. M., Simon L. S., Byrne M. S. Mononuclear cell-conditioned medium containing mononuclear cell factor (MCF), homologous with interleukin 1, stimulates collagen and fibronectin synthesis by adherent rheumatoid synovial cells: effects of prostaglandin E2 and indomethacin. Coll Relat Res. 1985 Mar;5(2):99–117. doi: 10.1016/s0174-173x(85)80033-9. [DOI] [PubMed] [Google Scholar]
  15. Nakata K., Bullough P. G. The injury and repair of human articular cartilage: a morphological study of 192 cases of coxarthrosis. Nihon Seikeigeka Gakkai Zasshi. 1986 Jul;60(7):763–775. [PubMed] [Google Scholar]
  16. Page Thomas D. P., King B., Stephens T., Dingle J. T. In vivo studies of cartilage regeneration after damage induced by catabolin/interleukin-1. Ann Rheum Dis. 1991 Feb;50(2):75–80. doi: 10.1136/ard.50.2.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Saklatvala J., Curry V. A., Sarsfield S. J. Purification to homogeneity of pig leucocyte catabolin, a protein that causes cartilage resorption in vitro. Biochem J. 1983 Nov 1;215(2):385–392. doi: 10.1042/bj2150385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 1986 Aug 7;322(6079):547–549. doi: 10.1038/322547a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sipe J. D., Bartle L. M., Loose L. D. Modification of proinflammatory cytokine production by the antirheumatic agents tenidap and naproxen. A possible correlate with clinical acute phase response. J Immunol. 1992 Jan 15;148(2):480–484. [PubMed] [Google Scholar]
  20. Tyler J. A. Articular cartilage cultured with catabolin (pig interleukin 1) synthesizes a decreased number of normal proteoglycan molecules. Biochem J. 1985 May 1;227(3):869–878. doi: 10.1042/bj2270869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tyler J. A. Chondrocyte-mediated depletion of articular cartilage proteoglycans in vitro. Biochem J. 1985 Jan 15;225(2):493–507. doi: 10.1042/bj2250493. [DOI] [PMC free article] [PubMed] [Google Scholar]

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