Insulin-like growth factor-I augments chondrocyte hypertrophy and reverses glucocorticoid-mediated growth retardation in fetal mice metatarsal cultures.
The study aims were to improve our understanding of the mechanisms of glucocorticoid-induced growth retardation at the growth plate and determine whether IGF-I could ameliorate the effects. Fetal mouse metatarsals were cultured for up to 10 d with dexamethasone (Dex; 10(-6) m) and/or IGF-I and GH (both at 100 ng/ml). Both continuous and alternate-day Dex treatment inhibited bone growth to a similar degree, whereas IGF-I alone or together with Dex caused an increase in bone growth. GH had no effects. These observations may be explained at the cellular level; cell proliferation within the growing bone was decreased by Dex and increased by IGF-I and these effects were more marked in the cells of the perichondrium than those in the growth plate. However, the most prominent observation was noted in the hypertrophic zone where all treatments containing IGF-I significantly increased (3-fold) the length of this zone, whereas Dex alone had no significant effect. In conclusion, Dex impaired longitudinal growth by inhibiting chondrocyte proliferation, whereas IGF-I stimulated chondrocyte hypertrophy and reversed the growth-inhibitory Dex effects. However, the IGF-I-mediated improvement in growth was at the expense of altering the balance between proliferating and hypertrophic chondrocytes within the metatarsal.
Mushtaq
T
T
Bone Biology Group, Roslin Institute, Edinburgh EH25 9PS, United Kingdom.
Bijman
P
P
Ahmed
S F
SF
Farquharson
C
C
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000196:embryology*; D002113:Calcification, Physiologic / Q000187:drug effects; D019902:Chondrocytes / Q000473:pathology*; D003907:Dexamethasone / Q000494:pharmacology; D004622:Embryo, Mammalian; D005938:Glucocorticoids / Q000494:pharmacology*; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008684:Metatarsus; D051379:Mice; D009924:Organ Culture Techniques; D014316:Tritium
D005938:Glucocorticoids; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D000469:Alkaline Phosphatase