In vitro culture of rabbit growth plate chondrocytes. 1. Age-dependence of response to fibroblast growth factor and "chondrocyte growth factor".

The growth-promoting effects of pituitary fibroblast growth factor (FGF) and "chondrocyte growth factor" (CGF), a contaminant of NIH-bovine TSH and ovine LH, were studied in monolayer and/or organ culture of epiphyseal plate chondrocytes of rabbits 1 day to 10 weeks old. The response to FGF (50 ng/ml) and CGF(TSH) and CGF(LH) (64 micrograms/ml) was age-dependent. In cultures from animals aged 4 weeks or older, the growth factors consistently stimulated DNA synthesis while decreasing incorporation of radiosulfate into matrix macromolecules. In organ cultures of the growth plate of rabbits less than 1 week old, FGF and NIH-TSH and LH actually diminished rather than promoted incorporation of 3H-thymidine. In organ culture the generation times of newborn rabbit proliferating zone chondrocytes, measured in vivo and in vitro by nuclear grain count dilution in 3H-thymidine autoradiographys, were 11 and 16 to 17 hours respectively. FGF and LH increased the generation time of 1- and 4-day old rabbit chondrocytes from 16 to over 24 hours. The stimulatory effect of CGF(TSH) in the older age group was much greater than that of NIH(LH). The dog-dose response curves of FGF and CGF(LH) were parallel, supporting Jones and Addison's view that the CGF activity of CGF(LH) derives from its content of FGF.