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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Figure 1

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Impaired growth of GHR–/– mice. (a) Growth curves of total body length (...
Impaired growth of GHR–/– mice. (a) Growth curves of total body length (left) and femoral length (right) in wild-type (+/+) and GHR–/– (–/–) mice (n = 8 per group). AP < 0.01, and BP < 0.001 vs. wild-type. (b) Toluidine blue–stained proximal tibial sections from wild-type and GHR–/– mice at 2, 3, 4, 6, and 10 weeks. Horizontal bars indicate limits of the proliferative (Prol) and hypertrophic (Hyp) zones. Scale bar, 100 μm. (c) Growth-plate and proliferative-zone width (Prol Z width) were reduced in GHR–/– mice (open) versus wild-type littermates (filled); n = 8 per group. AP < 0.05, BP < 0.01, and CP < 0.001 vs. wild-type. (d) Total femoral BMD (left) in 16-week-old littermates in wild-type (filled), heterozygote (gray, GHR+/–), and knockout (open, GHR–/–) mice. Proximal femoral BMC (right) at 8, 16, and 24 weeks of age in wild-type (filled), GHR+/– (gray), and GHR–/– (open) mice (n = 8 per group). AP < 0.05 and BP < 0.0001 vs. wild-type; CP < 0.001 and DP < 0.01 vs. same transgene group at previous time point.