Different regulation of clonal growth by transforming growth factor-beta 1 in human fetal articular and costal chondrocytes.
The variable affection of rib and limb growth in human skeletal dysplasias suggests the presence of site-specific regulatory mechanisms for chondrocyte proliferation. We therefore studied the clonal growth of normal human costal and articular chondrocytes from the same four fetuses (15 to 30 wk of gestation) in a semisolid medium (0.8% methylcellulose) with a basal supplementation of 5% heat-inactivated FCS. IGF-I[0.3-12.5 ng/mL (0.04-1.6 nmol/L)], IGF-II [0.3-12.5 ng/mL (0.04-1.7 nmol/L)], and hGH [0.5-25 ng/mL (0.02-1.1 nmol/L)] stimulated clonal growth of articular and costal chondrocytes without site-specific difference. In contrast, a significant difference was found for transforming growth factor-beta 1, which proved to be a potent growth factor for fetal articular chondrocytes but did not stimulate or only minimally stimulated fetal costal chondrocytes [p < 0.05 for 0.3 ng/mL (0.01 nmol/L) TGF-beta 1 and p < 0.01 for 1.25 ng/mL (0.05 nmol/L) TGF-beta 1 using paired t test]. Preincubation with an IGF-I receptor antibody (alpha IR-3) completely prevented the proliferative effect of IGF-I, IGF-II, and hGH, indicating that hGH acts via autocrine or paracrine induction of IGF. The antibody partly reduced TGF-beta 1 action on articular chondrocytes [p < 0.05 for 0.3 ng/mL (0.01 nmol/L) TGF-beta 1, NS for 1.25 ng/mL (0.05 nmol/L) TGF-beta 1 using paired t test]. These results indicate that TGF-beta 1 is involved in the regulation of human fetal growth and has a different effect in ribs and limbs.
Brenner
R E
RE
Universitätskinderklinik Abteilung I, Ulm, Germany.
Nerlich
A
A
Heinze
E
E
Vetter
U
U
Teller
W M
WM
D002356:Cartilage / Q000166:cytology / Q000187:drug effects*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D005333:Fetus / Q000166:cytology; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone