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Genome-wide screening in human growth plates during puberty in one patient suggests a role for RUNX2 in epiphyseal maturation

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In late puberty, estrogen decelerates bone growth by stimulating growth plate maturation. In this study, we analyzed the mechanism of estrogen action using two pubertal growth plate specimens of one girl at Tanner stage B2 and Tanner stage B3. Histological analysis showed that progression of puberty...

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Main Authors: Emons, Joyce (Author) , Dutilh, Bas E. (Author) , Decker, Eva (Author) , Pirzer, Heide (Author) , Sticht, Carsten (Author) , Gretz, Norbert (Author) , Rappold, Gudrun (Author) , Cameron, Ewan R. (Author) , Neil, James C. (Author) , Stein, Gary S. (Author) , Wijnen, Andre J. van (Author) , Wit, Jan Maarten (Author) , Post, Janine N. (Author) , Karperien, Marcel (Author)
Format: Article (Journal)
Language:English
Published: May 2011
In: The journal of endocrinology
Year: 2011, Volume: 209, Issue: 2, Pages: 245-254
ISSN:1479-6805
DOI:10.1530/JOE-10-0219
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1530/JOE-10-0219
Verlag, lizenzpflichtig, Volltext: https://joe.bioscientifica.com/view/journals/joe/209/2/245.xml
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Author Notes:Joyce Emons, Bas E. Dutilh, Eva Decker, Heide Pirzer, Carsten Sticht, Norbert Gretz, Gudrun Rappold, Ewan R. Cameron, James C. Neil, Gary S. Stein, Andre J. van Wijnen, Jan Maarten Wit, Janine N. Post and Marcel Karperien
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Summary:In late puberty, estrogen decelerates bone growth by stimulating growth plate maturation. In this study, we analyzed the mechanism of estrogen action using two pubertal growth plate specimens of one girl at Tanner stage B2 and Tanner stage B3. Histological analysis showed that progression of puberty coincided with characteristic morphological changes: a decrease in total growth plate height (P=0.002), height of the individual zones (P<0.001), and an increase in intercolumnar space (P<0.001). Microarray analysis of the specimens identified 394 genes (72% upregulated and 28% downregulated) that changed with the progression of puberty. Overall changes in gene expression were small (average 1.38-fold upregulated and 1.36-fold downregulated genes). The 394 genes mapped to 13 significantly changing pathways (P<0.05) associated with growth plate maturation (e.g. extracellular matrix, cell cycle, and cell death). We next scanned the upstream promoter regions of the 394 genes for the presence of evolutionarily conserved binding sites for transcription factors implicated in growth plate maturation such as estrogen receptor (ER), androgen receptor, ELK1, STAT5B, cyclic AMP response element (CREB), and RUNX2. High-quality motif sites for RUNX2 (87 genes), ELK1 (43 genes), and STAT5B (31 genes), but not ER, were evolutionarily conserved, indicating their functional relevance across primates. Moreover, we show that some of these sites are direct target genes of these transcription factors as shown by ChIP assays.
Item Description:Gesehen am 29.04.2022
Physical Description:Online Resource
ISSN:1479-6805
DOI:10.1530/JOE-10-0219

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