Interaction of epidermal growth factor and insulin-like growth factor-I in the regulation of growth plate chondrocytes.
The action of growth factors on the cells of the epiphyseal growth plate is an important mechanism in the regulation of skeletal growth. Insulin-like growth factor-I (IGF-I) is known to play a central role in the regulation of bone growth. In contrast, the role, if any, of epidermal growth factor (EGF) is not yet clear. In these studies, we tested the hypothesis that EGF interacts with IGF-I in the regulation of growth plate chondrocyte mitotic and metabolic activities. Chondrocytes isolated from bovine radioulnar growth plates and incubated in suspension culture were analyzed for their responsiveness to EGF with respect to synthesis of DNA, proteins, and proteoglycans, responsiveness to IGF-I, and ability to specifically bind [125I]IGF-I. Treatment of growth plate chondrocytes with maximally effective concentrations (10-100 ng/ml) of EGF produced a 16-27% increase in specific binding of [125I]IGF-I. Scatchard analysis indicated that this increase in specific binding was due to an increase in the number of receptors/cell with no change in receptor affinity. EGF stimulated protein synthesis by 30-35%. Pretreatment with EGF increased the responsiveness of chondrocytes to IGF-I, resulting in 90 and 60% augmentation of IGF-I-stimulated mitotic activity and proteoglycan synthesis, respectively. Given the prominent role of IGF-I in skeletal development and the presence of EGF in the growth plate, this study suggests an important role for interactions between these growth factors in the regulation of skeletal growth.
Bonassar
L J
LJ
Orthopaedic Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Trippel
S B
SB
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006132:Growth Plate / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008938:Mitosis / Q000187:drug effects; D011869:Radioligand Assay
D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I