کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1928393 | 1050352 | 2014 | 7 صفحه PDF | دانلود رایگان |

• Runx2 and Osterix double heterozygous embryos are generated.
• Hypertrophic chondrocytes are expanded and mineralized bones are reduced.
• Genes differentially regulated by Runx2/Osx deficiency are identified by microarray.
• 68 genes are upregulated and 18 genes downregulated.
The transcription factors, Runx2 and Osterix (Osx), act downstream in the BMP2 pathway, and they are essential for osteoblast differentiation and bone formation. While Runx2 expression is normal in Osx-null mice, Osx is not expressed in Runx2-null mice, indicating that Osx acts downstream of Runx2 during bone formation. Runx2 and Osx are also independently regulated during bone formation. To define the unknown correlation between Runx2 and Osx in the regulation of bone formation, we analyzed the bone of Runx2/Osx double heterozygotes generated by mating heterozygous Runx2 and Osx mice and elucidated the differential gene expressions due to the lack of Runx2 and Osx in bone. Compared to the Runx2 and Osx heterozygous embryos, Runx2/Osx double heterozygous embryos showed reduced bone length in the humerus and femur as well as hypoplastic or complete absence of the maxillary and palatine shelf, presphenoid bone, zygomatic bone, and tympanic ring. Severe inward bending was observed in the ribs and humerus. Histological analysis showed an expanded region of hypertrophic chondrocytes and a reduced area of mineralized bones in the Runx2/Osx double heterozygous embryos. DNA microarray analysis of the calvaria of embryos allowed gene classification based on similarities in the upregulated and downregulated expression patterns. Clusters 1 and 2 include 68 downregulated genes and 18 upregulated genes, respectively, in the Runx2/Osx double heterozygous embryos. Finally, the skeletal analysis and gene expression profiles obtained by clustering may facilitate the understanding of the correlation between Runx2 and Osx in skeletal development.
Journal: Biochemical and Biophysical Research Communications - Volume 451, Issue 3, 29 August 2014, Pages 442–448