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Open AccessArticle

Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature

1
Ecole de Kinésiologie et Récréologie, Faculté des Sciences de la Santé et Services Communautaires, Université de Moncton, Moncton, NB E1A 3E9, Canada
2
Embryologie Moléculaire et Cellulaire Animale, Institut des Sciences de la Vie, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium
3
Morphologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(10), 20386-20398; https://doi.org/10.3390/ijms141020386
Received: 13 June 2013 / Revised: 16 September 2013 / Accepted: 16 September 2013 / Published: 14 October 2013
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. However, the molecular pathways leading to such phenotype are still unknown. Using protein immunodetection and histological techniques comparing transgenic mice to controls, we show here that the persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively. Since Hoxa2 deregulation in mice induces a proportionate short stature phenotype mimicking human idiopathic conditions, our results give an insight into understanding proportionate short stature pathogenesis by highlighting molecular factors whose combined deregulation may be involved in such a disease. View Full-Text
Keywords: proportionate short stature; endochondral ossification; Hoxa2; chondrogenesis proportionate short stature; endochondral ossification; Hoxa2; chondrogenesis
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Deprez, P.M.L.; Nichane, M.G.; Lengelé, B.G.; Rezsöhazy, R.; Nyssen-Behets, C. Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature. Int. J. Mol. Sci. 2013, 14, 20386-20398.

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