Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1976 Dec;35(6):487–497. doi: 10.1136/ard.35.6.487

Effect of anti-inflammatory drugs on sulphated glycosaminoglycan synthesis in aged human articular cartilage.

L S McKenzie, B A Horsburgh, P Ghosh, T K Taylor
PMCID: PMC1006591  PMID: 1008617

Abstract

The anti-inflammatory drugs, sodium salicylate, indomethacin, hydrocortisone, ibuprofen, and flurbiprofen, were examined for their effects on sulphated glycosaminoglycan synthesis in aged human cartilage in vitro. Cartilage was obtained from femoral heads removed during surgery and drug effects were found to vary significantly from one head to another. Statistical analysis of the results showed that sodium salicylate exhibits concentration-dependent inhibition of glycosaminoglycan synthesis over the concentration range used. Indomethacin, hydrocortisone, and ibuprofen, at concentrations comparable to those attained in man, caused a statistically significant depression of sulphated glycosaminoglycan synthesis in cartilage from some femoral heads but not others, reflecting the variable response of human articular cartilage to anti-inflammatory drugs. Sodium salicylate and indomethacin at higher doses produced significant (Pless than 0-005) inhibition of sulphated glycosaminoglycan synthesis in all femoral heads studied. The results for flurbiprofen were less conclusive; this compound appears not to inhibit glycosaminoglycan synthesis over the concentration range used.

Full text

PDF
487

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arora S., Lahiri P. K., Sanyal R. K. The role of prostaglandin E1 in inflammatory process in the rat. Int Arch Allergy Appl Immunol. 1970;39(2-3):186–191. doi: 10.1159/000230346. [DOI] [PubMed] [Google Scholar]
  2. BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
  3. BOLLET A. J., HANDY J. R., STURGILL B. C. Chondroitin sulfate concentration and protein-polysaccharide composition of articular cartilage in osteoarthritis. J Clin Invest. 1963 Jun;42:853–859. doi: 10.1172/JCI104777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BOSTROEM H., BERNTSEN K., WHITEHOUSE M. W. BIOCHEMICAL PROPERTIES OF ANTI-INFLAMMATORY DRUGS-II. SOME EFFECTS ON SULPHATE-35S METABOLISM IN VIVO. Biochem Pharmacol. 1964 Mar;13:413–420. doi: 10.1016/0006-2952(64)90161-3. [DOI] [PubMed] [Google Scholar]
  5. Bjelle A. O., Antonopoulos C. A., Engfeldt B., Hjertquist S. O. Fractionation of the glycosaminoglycans of human articular cartilage on ecteola cellulose in ageing and in osteoarthrosis. Calcif Tissue Res. 1972;8(3):237–246. doi: 10.1007/BF02010142. [DOI] [PubMed] [Google Scholar]
  6. Bjelle A. O. Variations in content and composition of glycosaminoglycans within the articular cartilage of the lower femoral epiphysis of an adult. A pilot study. Scand J Rheumatol. 1974;3(2):81–88. doi: 10.3109/03009747409115806. [DOI] [PubMed] [Google Scholar]
  7. Bollet A. J., Nance J. L. Biochemical Findings in Normal and Osteoarthritic Articular Cartilage. II. Chondroitin Sulfate Concentration and Chain Length, Water, and Ash Content. J Clin Invest. 1966 Jul;45(7):1170–1177. doi: 10.1172/JCI105423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bullough P., Goodfellow J., O'Conner J. The relationship between degenerative changes and load-bearing in the human hip. J Bone Joint Surg Br. 1973 Nov;55(4):746–758. [PubMed] [Google Scholar]
  9. COLLINS D. H., McELLIGOTT T. F. Sulphate (35SO4) uptake by chondrocytes in relation to histological changes in osteoarthritic human articular cartilage. Ann Rheum Dis. 1960 Dec;19:318–330. doi: 10.1136/ard.19.4.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CURRAN R. C., GIBSON T. The uptake of labelled sulphate by human cartilage cells and its use as a test for viability. Proc R Soc Lond B Biol Sci. 1956 Mar 13;144(917):572–576. doi: 10.1098/rspb.1956.0012. [DOI] [PubMed] [Google Scholar]
  11. Chalmers I. M., Cathcart B. J., Kumar E. B., Dick W. C., Buchanan W. W. Clinico-pharmacological studies and clinical evaluation of flurbiprofen. A new non-steroidal antirheumatic agent. Ann Rheum Dis. 1972 Jul;31(4):319–324. doi: 10.1136/ard.31.4.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DAVIDSON E. A., SMALL W. Metabolism in vivo of connective-tissue mucopolysaccharides. II. Chondroitin sulfate B and hyaluronic acid of skin. Biochim Biophys Acta. 1963 Mar 5;69:453–458. doi: 10.1016/0006-3002(63)91293-9. [DOI] [PubMed] [Google Scholar]
  13. HOLT L. P., HAWKINS C. F. INDOMETHACIN: STUDIES OF ABSORPTION AND OF THE USE OF INDOMETHACIN SUPPOSITORIES. Br Med J. 1965 May 22;1(5446):1354–1356. doi: 10.1136/bmj.1.5446.1354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hardingham T. E., Muir H. Biosynthesis of proteoglycans in cartilage slices. Fractionation by gel chromatography and equilibrium density-gradient centrifugation. Biochem J. 1972 Feb;126(4):791–803. doi: 10.1042/bj1260791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jones I. L., Lemperg R. Chondroitin sulphate of calf knee-joint cartilage. Biochim Biophys Acta. 1975 Jun 12;392(2):310–318. doi: 10.1016/0304-4165(75)90012-4. [DOI] [PubMed] [Google Scholar]
  16. Kalbhen D. A., Karzel K., Domenjoz R. The inhibitory effects of some antiphlogistic drugs on the glucosamine incorporation into mucopolysaccharides synthesized by fibroblast cultures. Med Pharmacol Exp Int J Exp Med. 1967;16(3):185–189. doi: 10.1159/000136987. [DOI] [PubMed] [Google Scholar]
  17. Kaley G., Weiner R. Effect of prostaglandin E 1 on leukocyte migration. Nat New Biol. 1971 Nov 24;234(47):114–115. doi: 10.1038/newbio234114a0. [DOI] [PubMed] [Google Scholar]
  18. Karzel K., Domenjoz R. Actions of corticosteroids on mucopolysaccharide and protein metabolism of fibroblast monolayer cultures. Pharmacology. 1969;2(5):302–312. doi: 10.1159/000136033. [DOI] [PubMed] [Google Scholar]
  19. Kempson G. E., Muir H., Swanson S. A., Freeman M. A. Correlations between stiffness and the chemical constituents of cartilage on the human femoral head. Biochim Biophys Acta. 1970 Jul 21;215(1):70–77. doi: 10.1016/0304-4165(70)90388-0. [DOI] [PubMed] [Google Scholar]
  20. Lohmander S., Antonopoulos C. A., Friberg U. Chemical and metabolic heterogeneity of chondroitin sulfate and keratin sulfate in guinea pig cartilage and nucleus pulposus. Biochim Biophys Acta. 1973 Apr 28;304(2):430–448. doi: 10.1016/0304-4165(73)90263-8. [DOI] [PubMed] [Google Scholar]
  21. Lust G., Pronsky W. Glycosaminoglycan contents of normal and degenerative articular cartilage from dogs. Clin Chim Acta. 1972 Jul;39(2):281–286. doi: 10.1016/0009-8981(72)90045-9. [DOI] [PubMed] [Google Scholar]
  22. MATTHEWS B. F. Composition of articular cartilage in osteoarthritis; changes in collagen/chondroitin-sulphate ratio. Br Med J. 1953 Sep 19;2(4837):660–661. doi: 10.1136/bmj.2.4837.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mankin H. J., Dorfman H., Lippiello L., Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971 Apr;53(3):523–537. [PubMed] [Google Scholar]
  24. Mankin H. J. The reaction of articular cartilage to injury and osteoarthritis (first of two parts). N Engl J Med. 1974 Dec 12;291(24):1285–1292. doi: 10.1056/NEJM197412122912406. [DOI] [PubMed] [Google Scholar]
  25. Maroudas A., Muir H., Wingham J. The correlation of fixed negative charge with glycosaminoglycan content of human articular cartilage. Biochim Biophys Acta. 1969 May 6;177(3):492–500. doi: 10.1016/0304-4165(69)90311-0. [DOI] [PubMed] [Google Scholar]
  26. McDevitt C. A. Biochemistry of articular cartilage. Nature of proteoglycans and collagen of articular cartilage and their role in ageing and in osteoarthrosis. Ann Rheum Dis. 1973 Jul;32(4):364–378. doi: 10.1136/ard.32.4.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mills R. F., Adams S. S., Cliffe E. E., Dickinson W., Nicholson J. S. The metabolism of ibuprofen. Xenobiotica. 1973 Sep;3(9):589–598. doi: 10.3109/00498257309151547. [DOI] [PubMed] [Google Scholar]
  28. Moncada S., Ferreira S. H., Vane J. R. Prostaglandins, aspirin-like drugs and the oedema of inflammation. Nature. 1973 Nov 23;246(5430):217–219. doi: 10.1038/246217a0. [DOI] [PubMed] [Google Scholar]
  29. Muir H., Bullough P., Maroudas A. The distribution of collagen in human articular cartilage with some of its physiological implications. J Bone Joint Surg Br. 1970 Aug;52(3):554–563. [PubMed] [Google Scholar]
  30. Roach J. E., Tomblin W., Eyring E. J. Comparison of the effects of steroid, aspirin and sodium salicylate on articular cartilage. Clin Orthop Relat Res. 1975 Jan-Feb;(106):350–356. doi: 10.1097/00003086-197501000-00047. [DOI] [PubMed] [Google Scholar]
  31. Rokosovã B., Bentley J. P. The uptake of (14 C) glucose into rabbit ear cartilage proteoglycans isolated by differential extraction and by collagenase digestion. Biochim Biophys Acta. 1973 Feb 28;297(2):473–485. [PubMed] [Google Scholar]
  32. Simmons D. P., Chrisman O. D. Salicylate inhibition of cartilage degeneration. Arthritis Rheum. 1965 Oct;8(5):960–969. doi: 10.1002/art.1780080506. [DOI] [PubMed] [Google Scholar]
  33. Stockwell R. A., Scott J. E. Distribution of acid glycosaminoglycans in human articular cartilage. Nature. 1967 Sep 23;215(5108):1376–1378. doi: 10.1038/2151376a0. [DOI] [PubMed] [Google Scholar]
  34. TROWELL O. A. The culture of mature organs in a synthetic medium. Exp Cell Res. 1959 Jan;16(1):118–147. doi: 10.1016/0014-4827(59)90201-0. [DOI] [PubMed] [Google Scholar]
  35. Takeguchi C., Sih C. J. A rapid spectrophotometric assay for prostaglandin synthetase: application to the study of non-steroidal antiinflammatory agents. Prostaglandins. 1972 Sep;2(3):169–184. doi: 10.1016/s0090-6980(72)80021-2. [DOI] [PubMed] [Google Scholar]
  36. Tomlinson R. V., Ringold H. J. Relationship between inhibition of prostaglandin synthesis and drug efficacy: support for the current theory on mode of action of aspirin-like drugs. Biochem Biophys Res Commun. 1972 Jan 31;46(2):552–559. doi: 10.1016/s0006-291x(72)80174-8. [DOI] [PubMed] [Google Scholar]
  37. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  38. WHITEHOUSE M. W., BOSTROM H. The effect of some anti-inflammatory (anti-rheumatic) drugs on the metabolism of connective tissues. Biochem Pharmacol. 1962 Dec;11:1175–1201. doi: 10.1016/0006-2952(62)90196-x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES