Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Zonal differences in nitric oxide synthesis by bovine chrondrocytes exposed to interleukin-1

  • 22 Accesses

  • 46 Citations


To determine the role of nitric oxide (NO) in the inhibition of aggrecan synthesis, we measured levels of NO produced by bovine chondrocytes from different layers of articular cartilage in the presence of interleukin-1 (IL-1). Chondrocytes from the superficial layer showed a large increase in NO synthesis in response to IL-1. Although chondrocytes from the deep layer also produced NO in response to IL-1, the amount was less than that from the superficial layer. Enhanced NO production evoked by IL-1 was accompanied by a significant inhibition of aggrecan synthesis. These data suggest that chondrocytes in both superficial and deep layer of articular cartilage inhibit aggrecan synthesis with IL-1 via NO production. In addition, superficial layer cells respond to lower amounts of IL-1 with respect to NO-production and inhibition of proteoglycan synthesis.

This is a preview of subscription content, log in to check access.







  1. [1]

    Arend WP, Dayer JM. Inhibition of the production and effects of interleukin-1 and tumor necrosis factorα in rheumatoid arthritis. Arthr Rheum 1995;38:151–60.

  2. [2]

    Okada Y, Shinmei M, Tanaka O, Naka K, Kimura A, Nakanishi I, et al. Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. Lab Invest 1992;66:680–90.

  3. [3]

    Fukuda K, Dan H, Ohtani K, Tanaka S. Interleukin-1 inhibits keratan sulfate production by rabbit chondrocytes: possible role of prostaglandin E2. Inflamm Res 1995;44:178–81.

  4. [4]

    Van de Loo FS, Joosten LB, Van Lent PM, Arntz OJ, Van den Berg WB. Role of interleukin-1, tumor necrosis factorα, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Arthr Rheum 1995;38:164–72.

  5. [5]

    Aydelotte MB, Kuettner KE. Differences between sub-populations of cultures bovine articular chondrocytes. I. Morphology and cartilage matrix production. Connect Tissue Res 1988;18:205–22.

  6. [6]

    Aydelotte MB, Greenhill RR, Kuettner KE. Differences between sub-populations of cultures bovine articular chondrocytes. II. Proteoglycan metabolism. Connect Tissue Res 1988;18:223–34.

  7. [7]

    Aydelotte MB, Schumacher BL, Kuettner KE. Heterogeneity of articular cartilage. Articular Cartilage and Osteoarthritis. New York: Raven Press, 1992:237–49.

  8. [8]

    Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109–42.

  9. [9]

    Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: A physiologic messenger. Ann Int Med 1994;120:227–37.

  10. [10]

    Stadler J, Stefanovic-Racic M, Billiar TR, Curran RD, McIntyre LA, Georgescu HI et al. Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol 1991;147:3915–20.

  11. [11]

    Häuselmann HJ, Oppliger L, Michel BA, Stefanovic-Racic M, Evans CH. Nitric oxide and proteoglycan biosynthesis by human articular chondrocytes in alginate culture. FEBS Lett 1994;352:361–4.

  12. [12]

    Taskiran D, Stefanovic-Racic M, Georgescu H, Evans CH. Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1. Biochem Biophys Res Commun 1994;200:142–8.

  13. [13]

    Stefanovic-Racic M, Stadler J, Evans CH. Nitric oxide and arthritis. Arthr Rheum 1993;36:1036–44.

  14. [14]

    Fukuda K, Yamasaki H, Nagata Y, Motoyoshi H, Matsumura F, Kuno T, et al. Histamine Hl-receptormediated keratan sulfate secretion Am J Physiol 1991;261:C413–6.

  15. [15]

    Fukuda K, Matsumura F, Tanaka S. Histamine H2 receptor mediated keratan sulfate secretion in rabbit chondrocytes: role of cAMP. Am J Physiol 1993;265:C1653–7.

  16. [16]

    Archer S. Measurement of nitric oxide in biological models. FASEB J 1993;7:349–60.

  17. [17]

    Isaacson TC, Hampl V, Weir EK, Nelson DP, Archer SL. Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats. J Appl Physiol 1994;76:933–40.

  18. [18]

    Tyler JA. Articular cartilage cultured with catabolin (pig interleukin 1) synthesizes a decreased number of normal proteoglycan molecules. Biochem J 1985;227:869–78.

  19. [19]

    Siczkowski M, Watt FM. Subpopulations of chondrocytes from different zones of pig articular cartilage. J Cell Sci 1990;97:349–60.

  20. [20]

    Bayliss MT, Venn M, Maroudas A, Ali SY. Structure of proteoglycans from different layers of human articular cartilage. Biochem J 1983;209:387–400.

Download references

Author information

Correspondence to K. Fukuda.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fukuda, K., Kumano, F., Takayama, M. et al. Zonal differences in nitric oxide synthesis by bovine chrondrocytes exposed to interleukin-1. Inflamm Res 44, 434–437 (1995).

Download citation


  • Cartilage
  • Arthritis
  • Nitric oxide
  • Interleukin-1