Bone homeostasis in growth hormone receptor–null mice is restored by IGF-I but independent of Stat5
Natalie A. Sims, … , Roland Baron, Paul A. Kelly
Natalie A. Sims, … , Roland Baron, Paul A. Kelly
Published November 1, 2000
Citation Information: J Clin Invest. 2000;106(9):1095-1103. https://doi.org/10.1172/JCI10753.
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Article

Bone homeostasis in growth hormone receptor–null mice is restored by IGF-I but independent of Stat5

Abstract

Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The actions of GH are transduced by the Jak/Stat signaling pathway via Stat5, which is thought to regulate IGF-I expression. To determine the respective roles of GHR and IGF-I in bone growth and remodeling, we examined bones of wild-type, GHR knockout (GHR–/–), Stat5ab–/–, and GHR–/– mice treated with IGF-I. Reduced bone growth in GHR–/– mice, due to a premature reduction in chondrocyte proliferation and cortical bone growth, was detected after 2 weeks of age. Additionally, although trabecular bone volume was unchanged, bone turnover was significantly reduced in GHR–/– mice, indicating GH involvement in the high bone-turnover level during growth. IGF-I treatment almost completely rescued all effects of the GHR–/– on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes. Whereas bone length was reduced in Stat5ab–/– mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR–/– mice, indicating that the effects of GH in bone may not involve Stat5 activation.

Authors

Natalie A. Sims, Philippe Clément-Lacroix, Francesca Da Ponte, Yasmina Bouali, Nadine Binart, Richard Moriggl, Vincent Goffin, Karen Coschigano, Martine Gaillard-Kelly, John Kopchick, Roland Baron, Paul A. Kelly

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Longitudinal bone-growth and growth-plate dynamics are altered in 2-week...
Longitudinal bone-growth and growth-plate dynamics are altered in 2-week-old, but not mature, Stat5ab–/– mice. (a) Representative proximal tibial sections stained with toluidine blue from 2-, 6-, and 10-week-old wild-type and Stat5ab–/– mice. Horizontal bars indicate the limits of the proliferative (Prol) and hypertrophic (Hyp) zones. Scale bar, 100 μm. (b) Femoral length, femoral width, and widths of the proliferative and hypertrophic zones of the proximal tibial growth plate in wild-type and Stat5ab–/– mice at 2, 6, and 10 weeks of age; n = 6–12 per group. AP < 0.05, BP < 0.01 vs. control mice.