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Int. J. Mol. Sci. 2013, 14(10), 20386-20398; doi:10.3390/ijms141020386
Article

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

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Received: 13 June 2013; in revised form: 16 September 2013 / Accepted: 16 September 2013 / Published: 14 October 2013
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
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Abstract: 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.
Keywords: proportionate short stature; endochondral ossification; Hoxa2; chondrogenesis proportionate short stature; endochondral ossification; Hoxa2; chondrogenesis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

Deprez PML, Nichane MG, Lengelé BG, Rezsöhazy R, Nyssen-Behets C. Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature. International Journal of Molecular Sciences. 2013; 14(10):20386-20398.

Chicago/Turabian Style

Deprez, Pierre M.L.; Nichane, Miloud G.; Lengelé, Benoît G.; Rezsöhazy, René; Nyssen-Behets, Catherine. 2013. "Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature." Int. J. Mol. Sci. 14, no. 10: 20386-20398.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert