Fibroblast growth factors 1, 2, 17, and 19 are the predominant FGF ligands expressed in human fetal growth plate cartilage.
Fibroblast growth factors (FGF) regulate bone growth, but their expression in human cartilage is unclear. Here, we determined the expression of entire FGF family in human fetal growth plate cartilage. Using reverse transcriptase PCR, the transcripts for FGF1, 2, 5, 8-14, 16-19, and 21 were found. However, only FGF1, 2, 17, and 19 were detectable at the protein level. By immunohistochemistry, FGF17 and 19 were uniformly expressed within the growth plate. In contrast, FGF1 was found only in proliferating and hypertrophic chondrocytes whereas FGF2 localized predominantly to the resting and proliferating cartilage. In addition, only the 18 kD isoform of FGF2 was found in resting chondrocytes while proliferating chondrocytes also synthesized 22 kD and 24 kD FGF2, similar to in vitro cultivated chondrocytes. In cell growth experiments, FGF1, 2, and 17 but not FGF19 inhibited the proliferation of FGFR3-expressing rat chondrosarcoma chondrocytes (RCS) with relative potency FGF2 >> FGF1 = FGF17. We conclude that FGF1, 2, 17, and 19 are the predominant FGF ligands present in developing human cartilage that are, with the exception of FGF19, experimentally capable of inhibiting chondrocyte proliferation.
Krejci
Pavel
P
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. pavel.krejci@cshs.org
Krakow
Deborah
D
Mekikian
Pertchoui B
PB
Wilcox
William R
WR
D000818:Animals; D001483:Base Sequence; D001846:Bone Development; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004392:Dwarfism / Q000235:genetics; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006132:Growth Plate / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D009154:Mutation; D051381:Rats; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; C484724:FGF17 protein, human; C117476:FGF19 protein, human; D008024:Ligands; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3