Igf1 promotes longitudinal bone growth by insulin‐like actions augmenting chondrocyte hypertrophy

Abstract

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 3β (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., Zhou, J., Bondy, C. A. Igf1 promotes longitudinal bone growth by insulin‐like actions augmenting chondrocyte hypertrophy. FASEB J . 13, 1985–1990 (1999)