Inhibitory effects of basic fibroblast growth factor on chondrocyte differentiation.
The role of basic fibroblast growth factor (bFGF) and insulin-like growth factor I (IGF-I) in cartilage growth was studied in primary cultures of rat rib growth plate chondrocytes. Growth factors effects on expression of the proto-oncogene c-fos, DNA synthesis, differentiation, and morphological changes were analyzed by in situ hybridization, 3H-thymidine incorporation, and light and fluorescence microscopy. In serum-deprived cells, bFGF induced a transient expression of c-fos with a maximal effect 15-30 minutes after stimulation. After 24 h of culture it had a slightly lower stimulatory effect on DNA synthesis than IGF-I, but became a significantly more potent mitogen than IGF-I after 48 and 72 h. The stimulatory effect of bFGF on DNA synthesis coincided with a decrease in collagen type II and IGF-II expression. In contrast, IGF-I alone stimulated expression of these genes. In bFGF-treated cultures, cell morphology and the appearance of actin filaments was changed. Polygonal chondrocytes became elongated, fibroblast-like, and the smooth actin filaments were brush-like and disrupted. Addition of IGF-I reduced these changes without affecting c-fos expression induced by bFGF. Our results suggest that bFGF stimulates cell proliferation by preventing terminal differentiation of chondrocytes. This effect is mediated by induction of c-fos expression and a decrease in the steady-state levels of transcripts for collagen II and IGF-II.
Wroblewski
J
J
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Edwall-Arvidsson
C
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects*; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011519:Proto-Oncogenes; D051381:Rats; D012272:Ribs / Q000166:cytology / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D000199:Actins; D015345:Oligonucleotide Probes; D016760:Proto-Oncogene Proteins c-fos; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D004247:DNA; D013936:Thymidine