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Bone Abstracts (2013) 1 PP249 | DOI: 10.1530/boneabs.1.PP249

ECTS2013 Poster Presentations Chondrocytes and cartilage (20 abstracts)

Impairment of endochondral ossification by Hoxa2 overexpression: a plausible molecular explanation of idiopathic proportionate short stature

Pierre M L Deprez 1 , Miloud G Nichane 1, , Benoît Lengelé 1 , René Rezsöhazy 1, & Catherine Nyssen-Behets 1


1Pôle de Morphologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium; 2Institut des Sciences de la vie, Université Catholique de Louvainuvain-la-Neuve, Belgium.


Introduction: Using transgenic mice ectopically expressing Hoxa2 all along chondrogenesis, we previously associated the resulting animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was due to a negative influence of Hoxa2 in the very first step of endochondral ossification. As the molecular pathways underlying this pathogenesis are still unknown, we here tried to identify the impact of Hoxa2 overexpression on the main factors involved in endochondral ossification.

Materials and methods: In our transgenic mice Col2a1/Hoxa2-lacZ, Hoxa2 expression was induced in Col2a1 expressing territories and maintained thereafter, i.e. all over the endochondral bone pieces. Mice bearing the hβ-actin-lox-STOP-lox-Hoxa2-lacZ transgene only (βS-Hoxa2-lacZ) were considered controls. Using immunohistochemistry and western blotting, we compared the expression of Bapx1, Runx2, Sox5, Sox6, Bmpr1a, Foxc2, β1-integrin, Bmp7, Gdf10, Gdf5, Ihh, Wnt5a, Bmp4, Fgfr3, Gdf6, Meox1, Meox2, Pax1, PthrP, Msx1, Msx2, osteopontin, Pax9, S-100, and Sox9 in E13.5 transgenic and control mice.

Results: Persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the endochondral differentiation cascade, i.e. Sox9, Bapx1, Bmp7, Ihh, Msx1, Pax9, and Wnt5a. As a consequence, Hoxa2 misregulation in mice induces a proportionate short stature phenotype mimicking human idiopathic conditions.

Conclusions: Together, our results give insights for understanding proportionate short stature pathogenesis and reveal molecular mechanisms linking the activity of a Hox protein, Hoxa2, and its negative impact on endochondral skeleton development.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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