Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines

Arthritis Rheum. 1993 Feb;36(2):247-53. doi: 10.1002/art.1780360217.


Objective: To investigate the effects of hyaluronic acid (HA) on the release of proteoglycan by cultured rabbit chondrocytes.

Methods: Articular cartilage chondrocytes were isolated from the knee joints of New Zealand white rabbits. Proteoglycan synthesis after incubation with HA was determined by measuring 35S-sulfate incorporation. Cells incubated with HA were labeled with 3H-glucosamine and applied to a Sepharose CL-2B column. After incubation of confluent cells with 35S-sulfate and then with HA in various concentrations in the presence or absence of cytokines, proteoglycan release from the cell matrix layer was measured.

Results: HA (M(r) 3 x 10(5) to 19 x 10(5)), at 10 micrograms/ml to 1 mg/ml, had little effect on the incorporation of 35S-sulfate or 3H-glucosamine into cartilage matrix proteoglycans, or on the hydrodynamic size of proteoglycan monomers, in rabbit chondrocyte cultures. However, at 10-1,000 micrograms/ml, HA suppressed the release of 35S-proteoglycans from the cell matrix layer into the medium in the presence and absence of interleukin-1, tumor necrosis factor alpha, or basic fibroblast growth factor.

Conclusion: These results suggest that HA is a potent inhibitor of the displacement of matrix proteoglycan into culture medium.

MeSH terms

  • Animals
  • Cartilage, Articular / cytology*
  • Cells, Cultured
  • Culture Media / chemistry
  • Cytokines / pharmacology*
  • Extracellular Matrix / metabolism*
  • Fibroblast Growth Factor 2 / pharmacology
  • Hyaluronic Acid / pharmacology*
  • Male
  • Proteoglycans / analysis
  • Proteoglycans / biosynthesis*
  • Rabbits
  • Tumor Necrosis Factor-alpha / pharmacology


  • Culture Media
  • Cytokines
  • Proteoglycans
  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factor 2
  • Hyaluronic Acid