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Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Jul 1994; 53(7): 455–460.
PMCID: PMC1005370

Responsiveness of articular cartilage from normal and inflamed mouse knee joints to various growth factors.


OBJECTIVE--Disturbed anabolic signalling might contribute to the decreased chondrocyte proteoglycan (PG) synthesis during joint inflammation. Articular cartilage obtained from mouse knee joints with experimentally-induced arthritis exhibits a state of nonresponsiveness towards stimulation of chondrocyte PG synthesis by insulin-like growth factor-1 (IGF-1). Investigations were carried out on the role of other growth factors apart from IGF-1 on regulation of chondrocyte PG synthesis under pathological conditions, that is, during repair after IL-1 exposure as well as during early and later arthritis. METHODS--Mouse patellae were obtained from normal knee joints and joints injected with IL-1 or zymosan. The patellae were cultured with basic fibroblast growth factor [bFGF], platelet-derived growth factor [PDGF], epidermal growth factor [EGF] or transforming growth factor beta [TGF beta] for 24 hours in the presence or absence of IGF-1. Chondrocyte PG synthesis was measured by 35S-sulphate incorporation. RESULTS--In normal cartilage none of the tested growth factors elicited stimulatory effects on the chondrocyte PG synthesis as caused by IGF-1. EGF and TGF beta even caused significant inhibition of chondrocyte PG synthesis. Combination of bFGF or PDGF with IGF-1 exerted significant additional stimulation of the 35S-sulphate incorporation. IL-1 exposed cartilage displayed reactivity to IGF-1 as well as to the other growth factors similar to control cartilage. Cartilage obtained from joints with experimentally-induced arthritis exhibited a state of nonresponsiveness towards all individually tested growth factors as well as growth factor combinations. CONCLUSION--Arthritis causes nonresponsiveness to stimulation of chondrocyte PG synthesis by the tested growth factors, which might be caused by a general receptor function defect.

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Selected References

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  • van de Loo AA, van den Berg WB. Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation. Ann Rheum Dis. 1990 Apr;49(4):238–245. [PMC free article] [PubMed]
  • Verschure PJ, Van Noorden CJ. The effects of interleukin-1 on articular cartilage destruction as observed in arthritic diseases, and its therapeutic control. Clin Exp Rheumatol. 1990 May-Jun;8(3):303–313. [PubMed]
  • Bendtzen K, Petersen J, Halkjaer-Kristensen J, Ingemann-Hansen T. Interleukin-1-like activities in synovial fluids of patients with rheumatoid arthritis and traumatic synovitis. Rheumatol Int. 1985;5(2):79–82. [PubMed]
  • Benton HP, Tyler JA. Inhibition of cartilage proteoglycan synthesis by interleukin I. Biochem Biophys Res Commun. 1988 Jul 15;154(1):421–428. [PubMed]
  • Saxne T, Palladino MA, Jr, Heinegård D, Talal N, Wollheim FA. Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum. 1988 Aug;31(8):1041–1045. [PubMed]
  • Schalkwijk J, Joosten LA, van den Berg WB, van de Putte LB. Chondrocyte nonresponsiveness to insulin-like growth factor 1 in experimental arthritis. Arthritis Rheum. 1989 Jul;32(7):894–900. [PubMed]
  • Schalkwijk J, Joosten LA, van den Berg WB, van Wyk JJ, van de Putte LB. Insulin-like growth factor stimulation of chondrocyte proteoglycan synthesis by human synovial fluid. Arthritis Rheum. 1989 Jan;32(1):66–71. [PubMed]
  • Tyler JA. Insulin-like growth factor 1 can decrease degradation and promote synthesis of proteoglycan in cartilage exposed to cytokines. Biochem J. 1989 Jun 1;260(2):543–548. [PMC free article] [PubMed]
  • Kato Y, Hiraki Y, Inoue H, Kinoshita M, Yutani Y, Suzuki F. Differential and synergistic actions of somatomedin-like growth factors, fibroblast growth factor and epidermal growth factor in rabbit costal chondrocytes. Eur J Biochem. 1983 Jan 1;129(3):685–690. [PubMed]
  • Hiraki Y, Yutani Y, Takigawa M, Kato Y, Suzuki F. Differential effects of parathyroid hormone and somatomedin-like growth factors on the sizes of proteoglycan monomers and their synthesis in rabbit costal chondrocytes in culture. Biochim Biophys Acta. 1985 Jun 30;845(3):445–453. [PubMed]
  • Hiraki Y, Inoue H, Hirai R, Kato Y, Suzuki F. Effect of transforming growth factor beta on cell proliferation and glycosaminoglycan synthesis by rabbit growth-plate chondrocytes in culture. Biochim Biophys Acta. 1988 Apr 2;969(1):91–99. [PubMed]
  • Böhme K, Conscience-Egli M, Tschan T, Winterhalter KH, Bruckner P. Induction of proliferation or hypertrophy of chondrocytes in serum-free culture: the role of insulin-like growth factor-I, insulin, or thyroxine. J Cell Biol. 1992 Feb;116(4):1035–1042. [PMC free article] [PubMed]
  • Wroblewski J, Edwall C. PDGF BB stimulates proliferation and differentiation in cultured chondrocytes from rat rib growth plate. Cell Biol Int Rep. 1992 Feb;16(2):133–144. [PubMed]
  • Kato Y, Gospodarowicz D. Sulfated proteoglycan synthesis by confluent cultures of rabbit costal chondrocytes grown in the presence of fibroblast growth factor. J Cell Biol. 1985 Feb;100(2):477–485. [PMC free article] [PubMed]
  • Inoue H, Kato Y, Iwamoto M, Hiraki Y, Sakuda M, Suzuki F. Stimulation of cartilage-matrix proteoglycan synthesis by morphologically transformed chondrocytes grown in the presence of fibroblast growth factor and transforming growth factor-beta. J Cell Physiol. 1989 Feb;138(2):329–337. [PubMed]
  • Redini F, Daireaux M, Mauviel A, Galera P, Loyau G, Pujol JP. Characterization of proteoglycans synthesized by rabbit articular chondrocytes in response to transforming growth factor-beta (TGF-beta). Biochim Biophys Acta. 1991 Jul 10;1093(2-3):196–206. [PubMed]
  • O'Keefe RJ, Puzas JE, Brand JS, Rosier RN. Effects of transforming growth factor-beta on matrix synthesis by chick growth plate chondrocytes. Endocrinology. 1988 Jun;122(6):2953–2961. [PubMed]
  • Redini F, Galera P, Mauviel A, Loyau G, Pujol JP. Transforming growth factor beta stimulates collagen and glycosaminoglycan biosynthesis in cultured rabbit articular chondrocytes. FEBS Lett. 1988 Jul 4;234(1):172–176. [PubMed]
  • Morales TI, Roberts AB. Transforming growth factor beta regulates the metabolism of proteoglycans in bovine cartilage organ cultures. J Biol Chem. 1988 Sep 15;263(26):12828–12831. [PubMed]
  • Morales TI, Joyce ME, Sobel ME, Danielpour D, Roberts AB. Transforming growth factor-beta in calf articular cartilage organ cultures: synthesis and distribution. Arch Biochem Biophys. 1991 Aug 1;288(2):397–405. [PubMed]
  • Skantze KA, Brinckerhoff CE, Collier JP. Use of agarose culture to measure the effect of transforming growth factor beta and epidermal growth factor on rabbit articular chondrocytes. Cancer Res. 1985 Sep;45(9):4416–4421. [PubMed]
  • van der Kraan PM, Vitters EL, van den Berg WB. Inhibition of proteoglycan synthesis by transforming growth factor beta in anatomically intact articular cartilage of murine patellae. Ann Rheum Dis. 1992 May;51(5):643–647. [PMC free article] [PubMed]
  • van der Kraan P, Vitters E, van den Berg W. Differential effect of transforming growth factor beta on freshly isolated and cultured articular chondrocytes. J Rheumatol. 1992 Jan;19(1):140–145. [PubMed]
  • Hiraki Y, Inoue H, Asada A, Suzuki F. Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage. J Bone Miner Res. 1990 Oct;5(10):1077–1085. [PubMed]
  • Iwamoto M, Shimazu A, Nakashima K, Suzuki F, Kato Y. Reduction of basic fibroblasts growth factor receptor is coupled with terminal differentiation of chondrocytes. J Biol Chem. 1991 Jan 5;266(1):461–467. [PubMed]
  • van den Berg WB, Kruijsen MW, van de Putte LB, van Beusekom HJ, van der Sluis-van der Pol M, Zwarts WA. Antigen-induced and zymosan-induced arthritis in mice: studies on in vivo cartilage proteoglycan synthesis and chondrocyte death. Br J Exp Pathol. 1981 Jun;62(3):308–316. [PMC free article] [PubMed]
  • van Beuningen HM, Arntz OJ, van den Berg WB. In vivo effects of interleukin-1 on articular cartilage. Prolongation of proteoglycan metabolic disturbances in old mice. Arthritis Rheum. 1991 May;34(5):606–615. [PubMed]
  • Kato Y, Iwamoto M. Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation. J Biol Chem. 1990 Apr 5;265(10):5903–5909. [PubMed]
  • Osborn KD, Trippel SB, Mankin HJ. Growth factor stimulation of adult articular cartilage. J Orthop Res. 1989;7(1):35–42. [PubMed]
  • Burton-Wurster N, Lust G. Fibronectin and proteoglycan synthesis in long term cultures of cartilage explants in Ham's F12 supplemented with insulin and calcium: effects of the addition of TGF-beta. Arch Biochem Biophys. 1990 Nov 15;283(1):27–33. [PubMed]
  • Harvey AK, Stack ST, Chandrasekhar S. Differential modulation of degradative and repair responses of interleukin-1-treated chondrocytes by platelet-derived growth factor. Biochem J. 1993 May 15;292(Pt 1):129–136. [PMC free article] [PubMed]
  • Copray JC, Brouwer N, Prins AP, Jansen HW. Effects of polypeptide growth factors on mandibular condylar cartilage of the rat in vitro. J Biol Buccale. 1988 Jun;16(2):109–117. [PubMed]
  • Cuevas P, Burgos J, Baird A. Basic fibroblast growth factor (FGF) promotes cartilage repair in vivo. Biochem Biophys Res Commun. 1988 Oct 31;156(2):611–618. [PubMed]
  • Ogawa Y, Ksander GA, Pratt BM, Sawamura SJ, Ziman JM, Gerhardt CO, Avis PD, Murray MJ, McPherson JM. Differences in the biological activities of transforming growth factor-beta and platelet-derived growth factor in vivo. Growth Factors. 1991;5(1):57–68. [PubMed]

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