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 (Ig f1) is reputed to augment longitudinal bone growth by stimulating growth pl ate 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 cho ndrocytes differentiate normally in terms of expressing specialized protein s such as collagen X and alkaline phosphatase, but are smaller than wildtyp e at all levels of the hypertrophic zone, The terminal hypertrophic chondro cytes, which form the scaffold on which long bone growth extends, are reduc ed in linear dimension by 30% in Igf1 null mice, accounting for most of the ir decreased longitudinal growth, The expression of the insulin-sensitive g lucose transporter, GLUT4, is significantly decreased and the insulin-regul ated enzyme glycogen synthase kinase 3 beta (GSK3) is hypo-phosphorylated i n ISf1 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., Zho u, J., Bendy, C. A. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy.