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J Cell Biol. 1985 Feb 1; 100(2): 477–485.
PMCID: PMC2113445

Sulfated proteoglycan synthesis by confluent cultures of rabbit costal chondrocytes grown in the presence of fibroblast growth factor


We examined the effect of fibroblast growth factor (FGF) on proteoglycan synthesis by rabbit costal chondrocyte cultures maintained on plastic tissue culture dishes. Low density rabbit costal chondrocyte cultures grown in the absence of FGF gave rise at confluency to a heterogeneous cell population composed of fibroblastic cells and poorly differentiated chondrocytes. When similar cultures were grown in the presence of FGF, the confluent cultures organized into a homogenous cartilage-like tissue composed of rounded cells surrounded by a refractile matrix. The cell ultrastructure and that of the pericellular matrix were similar to those seen in vivo. The expression of the cartilage phenotype in confluent chondrocyte cultures grown from the sparse stage in the presence vs. absence of FGF was reflected by a fivefold increase in the rate of incorporation of [35S]sulfate into proteoglycans. These FGF effects were only observed when FGF was present during the cell logarithmic growth phase, but not when it was added after chondrocyte cultures became confluent. High molecular weight, chondroitin sulfate proteoglycans synthesized by confluent chondrocyte cultures grown in the presence of FGF were slightly larger in size than that produced by confluent cultures grown in the absence of FGF. The major sulfated glycosaminoglycans associated with low molecular weight proteoglycan in FGF-exposed cultures were chondroitin sulfate, while in cultures not exposed to FGF they were chondroitin sulfate and dermatan sulfate. Regardless of whether or not cells were grown in the presence or absence of FGF, the 6S/4S disaccharide ratio of chondroitin sulfate chains associated with high and low molecular weight proteoglycans synthesized by confluent cultures was the same. These results provide evidence that when low density chondrocyte cultures maintained on plastic tissue culture dishes are grown in the presence of FGF, it results in a stimulation of the expression and stabilization of the chondrocyte phenotype once cultures become confluent.

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Selected References

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  • Corvol MT, Malemud CJ, Sokoloff L. A pituitary growth-promoting factor for articular chondrocytes in monolayer culture. Endocrinology. 1972 Jan;90(1):262–271. [PubMed]
  • Jones KL, Addison J. Pituitary fibroblast growth factor as a stimulator of growth in cultured rabbit articular chondrocytes. Endocrinology. 1975 Aug;97(2):359–365. [PubMed]
  • Gospodarowicz D, Mescher AL. A comparison of the responses of cultured myoblasts and chondrocytes to fibroblast and epidermal growth factors. J Cell Physiol. 1977 Oct;93(1):117–127. [PubMed]
  • Kato Y, Nomura Y, Daikuhara Y, Nasu N, Tsuji M, Asada A, Suzuki F. Cartilage-derived factor (CDF) I. Stimulation of proteoglycan synthesis in rat and rabbit costal chondrocytes in culture. Exp Cell Res. 1980 Nov;130(1):73–81. [PubMed]
  • Phillips LS, Vassilopoulou-Sellin R. Somatomedins (first of two parts). N Engl J Med. 1980 Feb 14;302(7):371–380. [PubMed]
  • Prins AP, Lipman JM, McDevitt CA, Sokoloff L. Effect of purified growth factors on rabbit articular chondrocytes in monolayer culture. II. Sulfated proteoglycan synthesis. Arthritis Rheum. 1982 Oct;25(10):1228–1238. [PubMed]
  • Sachs BL, Goldberg VM, Moskowitz RW, Malemud CJ. Response of articular chondrocytes to pituitary fibroblast growth factor (FGF). J Cell Physiol. 1982 Jul;112(1):51–59. [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]
  • Kato Y, Gospodarowicz D. Growth requirements of low-density rabbit costal chondrocyte cultures maintained in serum-free medium. J Cell Physiol. 1984 Sep;120(3):354–363. [PubMed]
  • Jentzsch KD, Wellmitz G, Heder G, Petzold E, Buntrock P, Oehme P. A bovine brain fraction with fibroblast growth factor activity inducing articular cartilage regeneration in vivo. Acta Biol Med Ger. 1980;39(8-9):967–971. [PubMed]
  • Gospodarowicz D, Cheng J, Lui GM, Baird A, Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6963–6967. [PMC free article] [PubMed]
  • Gospodarowicz D, Mescher AL, Birdwell CR. Stimulation of corneal endothelial cell proliferations in vitro by fibroblast and epidermal growth factors. Exp Eye Res. 1977 Jul;25(1):75–89. [PubMed]
  • Gospodarowicz D, Hirabayashi K, Giguère L, Tauber JP. Factors controlling the proliferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture. J Cell Biol. 1981 Jun;89(3):568–578. [PMC free article] [PubMed]
  • Shimomura Y, Yoneda T, Suzuki F. Osteogenesis by chondrocytes from growth cartilage of rat rib. Calcif Tissue Res. 1975 Dec 22;19(3):179–187. [PubMed]
  • Ham RG, Sattler GL. Clonal growth of differentiated rabbit cartilage cells. J Cell Physiol. 1968 Oct;72(2):109–114. [PubMed]
  • Alvarado JA, Wood I, Polansky JR. Human trabecular cells. II. Growth pattern and ultrastructural characteristics. Invest Ophthalmol Vis Sci. 1982 Oct;23(4):464–478. [PubMed]
  • Yamagata T, Saito H, Habuchi O, Suzuki S. Purification and properties of bacterial chondroitinases and chondrosulfatases. J Biol Chem. 1968 Apr 10;243(7):1523–1535. [PubMed]
  • Mason RM, Kimura JH, Hascall VC. Biosynthesis of hyaluronic acid in cultures of chondrocytes from the Swarm rat chondrosarcoma. J Biol Chem. 1982 Mar 10;257(5):2236–2245. [PubMed]
  • Stevens RL, Hascall VC. Characterization of proteoglycans synthesized by rat chondrosarcoma chondrocytes treated with multiplication-stimulating activity and insulin. J Biol Chem. 1981 Feb 25;256(4):2053–2058. [PubMed]
  • Carrino DA, Lennon DP, Caplan AI. Extracellular matrix and the maintenance of the differentiated state: proteoglycans synthesized by replated chondrocytes and nonchondrocytes. Dev Biol. 1983 Sep;99(1):132–144. [PubMed]
  • Palmoski MJ, Goetinck PF. Synthesis of proteochondroitin sulfate by normal, nanomelic, and 5-bromodeoxyuridine-treated chondrocytes in cell culture. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3385–3388. [PMC free article] [PubMed]
  • Kimata K, Okayama M, Ooira A, Suzuki S. Heterogeneity of proteochondroitin sulfates produced by chondrocytes at different stages of cytodifferentiation. J Biol Chem. 1974 Mar 10;249(5):1646–1653. [PubMed]
  • Okayama M, Pacifici M, Holtzer H. Differences among sulfated proteoglycans synthesized in nonchondrogenic cells, presumptive chondroblasts, and chondroblasts. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3224–3228. [PMC free article] [PubMed]
  • Pacifici M, Fellini SA, Holtzer H, De Luca S. Changes in the sulfated proteoglycans synthesized by "aging" chondrocytes. I. Dispersed cultured chondrocytes and in vivo cartilages. J Biol Chem. 1981 Jan 25;256(2):1029–1037. [PubMed]
  • Kim JJ, Conrad HE. Proteochondroitin sulfate synthesis in subcultured chick embryo tibial chondrocytes. J Biol Chem. 1982 Feb 25;257(4):1670–1675. [PubMed]
  • Madsen K, Moskalewski S, von der Mark K, Friberg U. Synthesis of proteoglycans, collagen, and elastin by cultures of rabbit auricular chondrocytes--relation to age of the donor. Dev Biol. 1983 Mar;96(1):63–73. [PubMed]
  • Chacko S, Abbott J, Holtzer S, Holtzer H. The loss of phenotypic traits by differentiated cells. VI. Behavior of the progeny of a single chondrocyte. J Exp Med. 1969 Aug 1;130(2):417–442. [PMC free article] [PubMed]
  • Benya PD, Padilla SR, Nimni ME. Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture. Cell. 1978 Dec;15(4):1313–1321. [PubMed]
  • Vlodavsky I, Johnson LK, Greenburg G, Gospodarowicz D. Vascular endothelial cells maintained in the absence of fibroblast growth factor undergo structural and functional alterations that are incompatible with their in vivo differentiated properties. J Cell Biol. 1979 Nov;83(2 Pt 1):468–486. [PMC free article] [PubMed]
  • Gospodarowicz D, Vlodavsky I, Savion N. The extracellular matrix and the control of proliferation of vascular endothelial and vascular smooth muscle cells. J Supramol Struct. 1980;13(3):339–372. [PubMed]
  • Kimata K, Oike Y, Ito K, Karasawa K, Suzuki S. The occurrence of low buoyant density proteoglycans in embryonic chick cartilage. Biochem Biophys Res Commun. 1978 Dec 29;85(4):1431–1439. [PubMed]
  • Heinegård D, Paulsson M, Inerot S, Carlström C. A novel low-molecular weight chondroitin sulphate proteoglycan isolated from cartilage. Biochem J. 1981 Aug 1;197(2):355–366. [PMC free article] [PubMed]
  • Oegema TR, Jr, Thompson RC., Jr Characterization of a hyaluronic acid-dermatan sulfate proteoglycan complex from dedifferentiated human chondrocyte cultures. J Biol Chem. 1981 Jan 25;256(2):1015–1022. [PubMed]

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