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| Status |
Public on Jul 04, 2014 |
| Title |
Axin2/Runx2 mouse calvaria gene expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/- and double mutant Axin2-/-:Runx2+/- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation.
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| Overall design |
4 mice per genotype X 4 genotypes: wildtype (WT), Runx2+/- (R-Het), Axin2-/- (A-KO), Axin2-/-:Runx2+/- (A-KO:R-Het). Total = 16 samples
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| Contributor(s) |
Westendorf JJ, McGee-Lawrence ME |
| Citation(s) |
24973690 |
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| Submission date |
Jul 03, 2014 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Jie Sun |
| Organization name |
Mayo Clinic
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| Street address |
200 First Street SW
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| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE59083 |
Axin2/Runx2 mouse calvaria expression |
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| Relations |
| BioProject |
PRJNA254344 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59081_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE59081_non-normalized.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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