Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy.
Longitudinal bone growth, and hence stature, are functions of growth plate chondrocyte proliferation and hypertrophy. Insulin-like growth factor 1 (Igf1) is reputed to augment longitudinal bone growth by stimulating growth plate chondrocyte proliferation. In this study, however, we demonstrate that chondrocyte numbers and proliferation are normal in Igf1 null mice despite a 35% reduction in the rate of long bone growth. Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wild-type at all levels of the hypertrophic zone. The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth. The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3beta (GSK3) is hypo-phosphorylated in Igf1 null chondrocytes. Glycogen levels were significantly decreased and ribosomal RNA levels were reduced by almost 75% in Igf1 null chondrocytes. These data suggest that Igf1 promotes longitudinal bone growth by 'insulin-like' anabolic actions which augment chondrocyte hypertrophy.
Wang
J
J
Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zhou
J
J
Bondy
C A
CA
D000818:Animals; D002455:Cell Division; D019902:Chondrocytes / Q000473:pathology*; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006132:Growth Plate / Q000502:physiology*; D006984:Hypertrophy; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D012335:RNA, Ribosomal / Q000032:analysis
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012335:RNA, Ribosomal; C495693:Slc2a4 protein, mouse; D007334:Insulin-Like Growth Factor I; D006003:Glycogen