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Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth
Journal article   Open access   Peer reviewed

Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth

Shufang Wu, Wei Yang, Francesco De Luca and Francesco DeLuca
Endocrinology (Philadelphia), v 156(7), pp 2541-2551
Jul 2015
DOI: https://doi.org/10.1210/en.2014-1983
PMID: 25910049
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1210/en.2014-1983View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Animals Bone and Bones - drug effects Bone Development - drug effects Bone Morphogenetic Protein 2 - drug effects Bone Morphogenetic Protein 2 - genetics Cells, Cultured Chondrocytes - drug effects Chondrogenesis - drug effects Collagen Type X - drug effects Collagen Type X - genetics Growth Hormone - pharmacology Growth Plate - drug effects Growth Plate - metabolism Insulin-Like Growth Factor I - metabolism Insulin-Like Growth Factor II - metabolism Janus Kinase 2 - drug effects Janus Kinase 2 - metabolism Mice Mice, Knockout Phosphorylation Receptor, IGF Type 1 - genetics RNA, Messenger - drug effects RNA, Messenger - metabolism Transcription Factor RelA - drug effects Transcription Factor RelA - genetics
GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

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Web of Science research areas
Endocrinology & Metabolism
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