Stimulation of cartilage-matrix proteoglycan synthesis by morphologically transformed chondrocytes grown in the presence of fibroblast growth factor and transforming growth factor-beta

✍ Scribed by Hiroyuki Inoue; Yukio Kato; Masahiro Iwamoto; Yuji Hiraki; Mamoru Sakuda; Fujio Suzuki

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 1019 KB
• Volume: 138
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041380216

✦ Synopsis

The effects of transforming growth factor-beta (TGF-beta) on the synthesis of carii lage-r~ki~ rix protenglycan by cultured rabbit chondrocytes were examined. Rabbit chondrocytes were seeded at low density and exposed to a 1 :1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 medium supplemented with 0.5% fetal bovine serum, 1 % bovine serum albumin, 50 pdml ascorbic acid, and 2 x lop7 M hydrocortisone (Medium A). Various combinations of TGF-beta, insulin-like growth factor-I (IGF-I), and fibroblast growth factor (FGF) were also added to Medium A, and the chondrocytes were grown to confluency. Chondrocytes grown with TGF-beta or FGF alone became flat or libroblastic, those grown with FCF and TGF-beta became very elongated and formed distinct foci, and those grown with FCF and IGF-I showed the spherical configuration characteristic of overtly differentiated chondrocytes. Nevertheless, the incorporation of 'H with glucosamine into the large, chondroitin sulfate proteoglycan synthesized by cultures with FGF and TCF-beta was similar to that in cells grown with F C F and IGF-I and five times that in cells cultured with FCF alone. The increases in incorporation of 'H reflected real increases in proteoglycan synthesis, k a u s e cherriic:al analyses showed an increase in the accumulation of macromolecules containing uronic acid in cultures with FGF and TGF-beta or with FGF and IGF-I. However, FCF in combination with eithcr TGF-beta or ICF-l had little effect on the incorporation of 'H into small proteoglycans or hyaluronic acid. These results indicate that chondrocytes morphologically transformed with TCF-beta and FCF fully express the differentiated proteoglycan phenotype rather than the transformed glycosaminoglycan phenotype.