Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 Aug;50(8):1712–1719. doi: 10.1172/JCI106660

The Glycosaminoglycans of Normal and Arthritic Cartilage

Henry J Mankin 1,2, Louis Lippiello 1,2
PMCID: PMC442071  PMID: 4255496

Abstract

The cartilages from the hip joints of 13 normal and 15 osteoarthritic humans were analyzed for glycosaminoglycan content and distribution. The GAGs were separated by elution with CPC on a short cellulose column by the technique of Svejcar and Robertson after digestion of the tissue with pronase and papain. The eluates were identified by a variety of methods including determination of molar ratios, N-acetyl-hexosamine determinations after hyaluronidase treatment and thin-layer chromatography of unhydrolyzed and hydrolyzed GAGs.

From the data obtained, it was demonstrated that cartilage from arthritic patients showed a significant increase in the concentration of chondroitin 4-sulfate and a significant decrease in keratan sulfate, with only slight changes in the total amount of GAG present. Calculations of the molar ratios showed variation in the sulfation with chondroitin 4-sulfate appearing in the “supersulfated” state in the arthritic cartilage.

The data lead to speculation regarding the process of osteoarthritis, and it is concluded that the changes seen are more likely to represent an altered pattern of synthesis rather than selective degradation. Since the changes suggest a younger cartilage, a theory is advanced that the chondrocyte responds to the chronic stress of osteoarthritis by modulation to a chondroblastic phase.

Full text

PDF
1713

Selected References

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

  1. ANDERSON C. E., LUDOWIEG J., HARPER H. A., ENGLEMAN E. P. THE COMPOSITION OF THE ORGANIC COMPONENT OF HUMAN ARTICULAR CARTILAGE. RELATIONSHIP TO AGE AND DEGENERATIVE JOINT DISEASE. J Bone Joint Surg Am. 1964 Sep;46:1176–1183. [PubMed] [Google Scholar]
  2. ANTONOPOULOS C. A., GARDELL S., SZIRMAI J. A., DETYSSONSK E. R. DETERMINATION OF GLYCOSAMINOGLYCANS (MUCOPOLYSACCHARIDES) FROM TISSUE ON THE MICROGRAM SCALE. Biochim Biophys Acta. 1964 Mar 2;83:1–19. doi: 10.1016/0926-6526(64)90045-x. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Bollet A. J. An essay on the biology of osteoarthritis. Arthritis Rheum. 1969 Apr;12(2):152–163. doi: 10.1002/art.1780120212. [DOI] [PubMed] [Google Scholar]
  6. Bollet A. J. Connective tissue polysaccharide metabolism and the pathogenesis of osteoarthritis. Adv Intern Med. 1967;13:33–60. [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. 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]
  9. Chrisman O. D. Biochemical aspects of degenerative joint disease. Clin Orthop Relat Res. 1969 May-Jun;64:77–86. [PubMed] [Google Scholar]
  10. DAVIDSON E. A., SMALL W. Metabolism in vivo of connective-tissue mucopolysaccharides. III. Chondroitin sulfate and keratosulfate of cartilage. Biochim Biophys Acta. 1963 Mar 5;69:459–463. doi: 10.1016/0006-3002(63)91294-0. [DOI] [PubMed] [Google Scholar]
  11. Hjertquist S. O., Vejlens L. The glycosaminoglycans of dog compact bone and epiphyseal cartilage in the normal state and in experimental hyperparathyroidism. Calcif Tissue Res. 1968 Dec 18;2(4):314–333. doi: 10.1007/BF02279220. [DOI] [PubMed] [Google Scholar]
  12. JEANLOZ R. W. The nomenclature of mucopolysaccharides. Arthritis Rheum. 1960 Jun;3:233–237. doi: 10.1002/art.1780030306. [DOI] [PubMed] [Google Scholar]
  13. KAPLAN D., MEYER K. Ageing of human cartilage. Nature. 1959 May 2;183(4670):1267–1268. doi: 10.1038/1831267a0. [DOI] [PubMed] [Google Scholar]
  14. LOEWI G. Changes in the ground substance of ageing cartilage. J Pathol Bacteriol. 1953 Apr;65(2):381–388. doi: 10.1002/path.1700650211. [DOI] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Lippiello L., Mankin H. J. Thin-layer chromatographic separation of the isomeric chondroitin sulfates, dermatan sulfate, and keratan sulfate. Anal Biochem. 1971 Jan;39(1):54–58. doi: 10.1016/0003-2697(71)90460-x. [DOI] [PubMed] [Google Scholar]
  17. MATHEWS M. B., INOUYE M. The determination of chondroitin sulfate C-type polysaccharides in mixtures with other acid mucopolysaccharides. Biochim Biophys Acta. 1961 Nov 11;53:509–513. doi: 10.1016/0006-3002(61)90209-8. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Mankin H. J., Lippiello L. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. J Bone Joint Surg Am. 1970 Apr;52(3):424–434. [PubMed] [Google Scholar]
  20. Mathews M. B., Cifonelli J. A. Comparative biochemistry of keratosulfates. J Biol Chem. 1965 Nov;240(11):4140–4145. [PubMed] [Google Scholar]
  21. Mathews M. B., Glagov S. Acid mucopolysaccharide patterns in aging human cartilage. J Clin Invest. 1966 Jul;45(7):1103–1111. doi: 10.1172/JCI105416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Muir H. Chemistry and metabolism of connective tissue glycosaminoglycans (mucopolysaccharides). Int Rev Connect Tissue Res. 1964;2:101–154. doi: 10.1016/b978-1-4831-6751-0.50009-4. [DOI] [PubMed] [Google Scholar]
  23. REISSIG J. L., STORMINGER J. L., LELOIR L. F. A modified colorimetric method for the estimation of N-acetylamino sugars. J Biol Chem. 1955 Dec;217(2):959–966. [PubMed] [Google Scholar]
  24. RONDLE C. J., MORGAN W. T. The determination of glucosamine and galactosamine. Biochem J. 1955 Dec;61(4):586–589. doi: 10.1042/bj0610586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. SHETLAR M. R., MASTERS Y. F. Effect of age on polysaccharide composition of cartilage. Proc Soc Exp Biol Med. 1955 Oct;90(1):31–33. doi: 10.3181/00379727-90-21931. [DOI] [PubMed] [Google Scholar]
  26. STIDWORTHY G., MASTERS Y. F., SHETLAR M. R. The effect of aging on mucopolysaccharide composition of human costal cartilage as measured by hexosamine and uronic acid content. J Gerontol. 1958 Jan;13(1):10–13. doi: 10.1093/geronj/13.1.10. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Stockwell R. A., Scott J. E. Observations on the acid glycosaminoglycan (mucopolysaccharide) content of the matrix of aging cartilage. Ann Rheum Dis. 1965 Jul;24(4):341–350. doi: 10.1136/ard.24.4.341. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES