Skip to main content

Proteoglycan loss and subsequent replenishment in articular cartilage after a mild arthritic insult by IL-1 in mice: Impaired proteoglycan turnover in the recovery phase

Agents and Actions volume 41, pages 200–208 (1994)Cite this article

Abstract

The reparative responses of articular cartilage after an arthritic insult have not been studied extensively to this day. In the present study, we injected interleukin-1 (IL-1) into knee joints of mice to provoke a mild and transient arthritic insult, and characterized both the catabolic and the subsequent recovery phase. In the catabolic phase, which lasted 2 days after IL-1 injection, proteoglycan (PG) breakdown was profoundly accelerated and PG synthesis was markedly inhibited. Sulfation and polysaccharide synthesis were not affected, yet the number of chondroitin sulfate chains was decreased. The general chondrocyte protein synthesis was not inhibited by IL-1. IL-1 injected every other day for a total of three injections prolonged this catabolic phase and resulted in frank loss of articular cartilage proteoglycans. In the recovery phase, started 3 days after IL-1, PG synthesis was enhanced (1.7 times the normal) and proteoglycans had normal hydrodynamic properties. Remarkably, PG degradation was significantly decreased (approximately 50% of the normal). Zymographic analysis demonstrated enhanced expression of gelatinolytic activities in the extracts of the articular tissues shortly after IL-1 exposure and decreased levels in the recovery phase. We found that the overshoot of PG synthesis and impaired degradation act together to facilitate full cartilage repair 7 days after the last of the three IL-1 injections.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. A. I. Caplan,Cartilage. Sci. Am.521, 82–90 (1984).

    Google Scholar 

  2. N. D. Broom and H. Silyn-Roberts,Collagen-collagen versus collagen-proteoglycan interactions in the determination of cartilage strength. Arth. Rheum.33, 1512–1517 (1990).

    Google Scholar 

  3. T. I. Morales and V. C. Hascall,Factors involved in the regulation of proteoglycan metabolism in articular cartilage. Arth. Rheum.32, 1197–1201 (1989).

    Google Scholar 

  4. A. A. J. van de Loo and W. B. van den Berg,Effects of murine recombinant interleukin 1 on synovial joints in mice: Measurements of patellar cartilage metabolism and joint inflammation. Ann. Rheum. Dis.49, 238–245 (1990).

    PubMed  Google Scholar 

  5. H. M. van Beuningen, O. J. Arntz and W. B. van den Berg,In vivo effects of interleukin-1 on articular cartilage, Prolongation of proteoglycan metabolic disturbances in old mice. Arth. Rheum.34, 606–615 (1991).

    Google Scholar 

  6. F. A. J. van de Loo, O. J. Arntz, I. G. Otterness and W. B. van den Berg,Protection against cartilage proteoglycan synthesis inhibition by antiinterleukin 1 antibodies in experimental arthritis. J. Rheumatol.19, 348–356 (1992).

    PubMed  Google Scholar 

  7. F. A. van de Loo, O. J. Arntz, I. G. Otterness and W. B. van den Berg,Modulation of cartilage destruction in murine arthritis with anti-Il-1 antibodies. Agents and Actions39, C211-C214 (1993).

    Article  PubMed  Google Scholar 

  8. W. B. van den Berg, F. A. J. van de Loo, P. L. E. M. van Lent and L. A. B. Joosten,Mechanism of cartilage destruction in joint inflammation. Agents and Actions39, 49–60 (1993).

    Article  Google Scholar 

  9. M. E. Adams and K. D. Brandt,Hypertrophic repair of canine articular cartilage in osteoarthritis after anterior cruciate ligament transection. J. Rheumatol.18, 428–435 (1991).

    PubMed  Google Scholar 

  10. G. O. Daumy, J. M. Merenda, A. S. McCall, G. C. Andrews, A. E. Franke, K. F. Geoghegan and I. G. Otterness,Isolation and characterization of biologically active murine interleukin-1α derived from, expression of a synthetic gene in Escherichia coli. Biochem. Biophys. Acta998, 32–42 (1989).

    PubMed  Google Scholar 

  11. B. J. de Vries, W. B. van den Berg, E. Vitters and L. B. A. van de Putte, Quantitation of glycosaminoglycan metabolism in anatomically intact articular cartilage of the mouse: In vitro and in vivo studies with35S-sulfate,3H-glucosamine and3H-acetate. Rheumatol. Int.6, 27–281 (1987).

    Google Scholar 

  12. R. W. Farndale, D. J. Buttle and A. J. Barrett, “Improved quantitation of sulfated glycosaminoglycans by use of dimethylmethylene blue. Biochem. Biophys. Acta883, 173–177 (1986).

    PubMed  Google Scholar 

  13. R. L. Y. Sah, A. J. Grodzinsky, A. H. K. Plaas and J. D. Sandy,Effects of tissue compression on the hyaluronate-binding proper ties of newly synthesized proteoglycans in cartilage explants. Biochem. J.267, 8033–808 (1990).

    Google Scholar 

  14. P. M. van der Kraan, E. L. Vitters, N. S. Postma, J. Verbunt and W. B. van den Berg,Maintenance of the synthesis of large proteoglycans in anatomically intact murine articular cartilage by steriods and insulin-like growth factor. 1. Ann. Rheum. Dis.52, 734–741 (1993).

    PubMed  Google Scholar 

  15. C. Heussen and E. B. Dowdle,Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecylsulfate and copolymerized substrates. Anal. Biochem.102, 196–202 (1980).

    Article  PubMed  Google Scholar 

  16. A. D. Elbstein,The tunicamycin-useful tools for studies on glycoproteins. Trends Biochem. Sci.6, 219–221 (1981).

    Article  Google Scholar 

  17. G. Venn and R. M. Mason,Biosynthesis and metabolism in vivo of invertebral-disc proteoglycans in the mouse. Biochem. J.215, 217–225 (1983).

    PubMed  Google Scholar 

  18. K. S. Rostand, J. R. Baker, B. Caterson and J. E. Christner,Isolation and characterization of mouse articular cartilage proteoglycans using preformed CsCl density gradients in the Beckman airfuge. J. Biol. Chem.257, 703–707 (1982).

    PubMed  Google Scholar 

  19. K. S. Rostand, J. R. Baker, B. Caterson and J. E. Christner,Articular cartilage proteoglycans from normal and osteoarthritic mice. Arth. Rheum.29, 95–105 (1986).

    Google Scholar 

  20. H. P. Benton and J. A. Tyler,Inhibition of cartilage proteoglycan synthesis by interleukin-1. Biochem. Biophys. Res. Commun.154, 421–428 (1988).

    Article  PubMed  Google Scholar 

  21. T. I. Morales and V. C. Hascall,Effects of interleukin-1 and lipopolysaccharides on protein and carbohydrate metabolism in bovine articular cartilage organ cultures. Conn. Tissue Res.19, 225–275 (1989).

    Google Scholar 

  22. D. Page-Thomas, B. King, T. Stephens and J. T. Dingle,In vivo studies of cartilage regeneration after damage induced by catabolin/interleukin-1. Ann. Rheum. Dis.50, 75–80 (1991).

    PubMed  Google Scholar 

  23. R. A. Stockwell,The interrelationship of cell density and cartilage thickness in mammalian articular cartilage. J. Anat.109, 411–421 (1971).

    PubMed  Google Scholar 

  24. S. Chandrasekhar, A. K. Harvey and P. S. Hrubey,Intra-articular administration of interleukin-1 causes prolonged suppression of cartilage proteoglycan synthesis in rats. Matrix11, 1–10 (1992).

    Google Scholar 

  25. F. Boussidan and A. M. Nahir,Altered chondrocytic oxidative metabolism during the restoration of depleted intercellular matrix. J. Exp. Pathol (Oxford)71, 195–402 (1990).

    Google Scholar 

  26. A. J. Fosang, J. A. Tyler and T. E. Hardingham,Effect of interleukin-1 and insulin like growth factor-1 on the release of proteoglycan components and hyaluronan from pig articular cartilage in explant culture. Matrix11, 17–24 (1991).

    PubMed  Google Scholar 

  27. C. Hughes, G. Murphy and T. E. Hardingham,Metalloproteinase digestion of cartilage proteoglycan. Pattern of cleavage by stromelysin and susceptibility to collagenase. Biochem. J.279, 733–739 (1991).

    PubMed  Google Scholar 

  28. J. D. Sandy, R. E. Boynton and C. R. Flannary,Analysis of catabolism of aggregan in cartilage explants by quantitation of peptides from the three globular domains. J. Biol.266, 8683–8685 (1991).

    Google Scholar 

  29. V. Lefebvre, C. Peeters-Joris and G. Vaes,Production of gelatin-degrading matrix metalloproteinases (‘type IV collagenases’) and inhibitors by articular chondrocytes during their dedifferentiation by serial subcultures and under stimulation by interleukin-1 and tumor necrosis factor α. Biochim. Biophys. Acta1094, 8–18 (1991).

    Article  PubMed  Google Scholar 

  30. A. J. P. Docherty and G. Murphy,The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. Ann. Rheum. Dis.49, 469–479 (1990).

    PubMed  Google Scholar 

  31. A. C. Arner, and M. A. Pratta,Independent effects of interleukin-1 on proteoglycan breakdown, proteoglycan synthesis, and prostaglandin E2 release from cartilage in organ culture. Arth. Rheum.32, 288–297 (1989).

    Google Scholar 

Download references

Author information

Affiliations

  1. Department of Rheumatology, University Hospital Nijmegen, Geert Grooteplein zuid 8, 6525 GA, Nijmegen, The Netherlands

    A. A. J. van de Loo, O. J. Arntz & W. B. van den Berg

  2. Department of Immunology and Infectious Diseases, Pfizer Inc., 06340, Groton, CT, USA

    I. G. Otterness

Authors
  1. A. A. J. van de Loo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. J. Arntz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. G. Otterness
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. B. van den Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

van de Loo, A.A.J., Arntz, O.J., Otterness, I.G. et al. Proteoglycan loss and subsequent replenishment in articular cartilage after a mild arthritic insult by IL-1 in mice: Impaired proteoglycan turnover in the recovery phase. Agents and Actions 41, 200–208 (1994). https://doi.org/10.1007/BF02001917

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02001917

Key words

  • Patella
  • Chondrocyte metabolism
  • Gelatinase-activities
  • Zymography
  • Glycosaminoglycan
  • Interleukin-1