title: Insulin-like growth factor-I and fibroblast growth factor, but not growth hormone, affect growth plate chondrocyte proliferation.
abstract: Of the many factors that regulate linear growth, IGF-I has a central role in epiphyseal chondrocyte development. Whether IGF-I is solely of systemic or also of local origin is uncertain, as is how other growth factors interact with IGF-I at the growth plate. We studied the proliferative effects of IGF-I on juvenile bovine epiphyseal chondrocytes fractionated by density gradient centrifugation. Cell density correlated with size, glycogen content, and gene expression patterns. There was a gradient of response to IGF-I, with the greatest proliferative response in high-density cells corresponding to the reserve zone, as measured by [3H]thymidine uptake. Low-density (hypertrophic zone) cells proliferated only when exposed to IGF-I and basic fibroblast growth factor (FGF). The gradient of IGF-I response correlated with [125I]IGF-I binding as determined by Scatchard analysis: IGF-I receptor number was 10-fold greater in reserve zone cells than in hypertrophic cells. When exposed to basic FGF for 24 hours, IGF-I binding in hypertrophic cells increased 3-fold. In contrast, no specific binding of GH was demonstrated in juvenile bovine chondrocytes. GH produced neither signal transducer and activator of transcription phosphorylation, increased proliferation, nor increased IGF-I mRNA levels in any chondrocyte fraction. IGF-I mRNA levels were extremely low at 800-1100 copies/microg 18S RNA in bovine chondrocytes. These results suggest that the major regulator of chondrocyte proliferation is systemic IGF-I; FGFs may influence the actions of IGF-I at the growth plate by altering its receptor number in chondrocytes.
authors: Division of Pediatric Endocrinology, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9063, USA. michele.hutchison@utsouthwestern.edu
authors: Michele R
authors: MR
authors: Hutchison
authors: Mary H
authors: MH
authors: Bassett
authors: Perrin C
authors: PC
authors: White
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015153:Blotting, Western; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D024043:Collagen Type II; D053823:Hedgehog Proteins; D050799:STAT5 Transcription Factor; D013002:Somatomedins; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1