Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature
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 o...
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| Format: | Article |
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MDPI AG
2013-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/14/10/20386 |
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| author | Catherine Nyssen-Behets René Rezsöhazy Benoît G. Lengelé Pierre M. L. Deprez Miloud G. Nichane |
| author_facet | Catherine Nyssen-Behets René Rezsöhazy Benoît G. Lengelé Pierre M. L. Deprez Miloud G. Nichane |
| author_sort | Catherine Nyssen-Behets |
| collection | DOAJ |
| description | 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. |
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| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T05:32:35Z |
| publishDate | 2013-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ede4c38c8431475ba8a025e5d5e1e82d2022-12-22T03:00:23ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-10-011410203862039810.3390/ijms141020386Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short StatureCatherine Nyssen-BehetsRené RezsöhazyBenoît G. LengeléPierre M. L. DeprezMiloud G. NichaneIn 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.http://www.mdpi.com/1422-0067/14/10/20386proportionate short statureendochondral ossificationHoxa2chondrogenesis |
| spellingShingle | Catherine Nyssen-Behets René Rezsöhazy Benoît G. Lengelé Pierre M. L. Deprez Miloud G. Nichane Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature International Journal of Molecular Sciences proportionate short stature endochondral ossification Hoxa2 chondrogenesis |
| title | Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature |
| title_full | Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature |
| title_fullStr | Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature |
| title_full_unstemmed | Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature |
| title_short | Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature |
| title_sort | molecular study of a hoxa2 gain of function in chondrogenesis a model of idiopathic proportionate short stature |
| topic | proportionate short stature endochondral ossification Hoxa2 chondrogenesis |
| url | http://www.mdpi.com/1422-0067/14/10/20386 |
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