Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5.
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.
Sims
N A
NA
Institut Nationale de la Santé et de la Recherche Médicale (INSERM), Unité 344, Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France.
Clément-Lacroix
P
P
Da Ponte
F
F
Bouali
Y
Y
Binart
N
N
Moriggl
R
R
Goffin
V
V
Coschigano
K
K
Gaillard-Kelly
M
M
Kopchick
J
J
Baron
R
R
Kelly
P A
PA
D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008894:Milk Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone