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Publication : Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice.

First Author  Nakamura E Year  2021
Journal  Commun Biol Volume  4
Issue  1 Pages  1258
PubMed ID  34732852 Mgi Jnum  J:316165
Mgi Id  MGI:6825929 Doi  10.1038/s42003-021-02793-9
Citation  Nakamura E, et al. (2021) Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice. Commun Biol 4(1):1258
abstractText  Endochondral ossification is regulated by transcription factors that include SRY-box transcription factor 9, runt-related protein 2 (Runx2), and Osterix. However, the sequential and harmonious regulation of the multiple steps of endochondral ossification is unclear. This study identified zinc finger homeodomain 4 (Zfhx4) as a crucial transcriptional partner of Osterix. We found that Zfhx4 was highly expressed in cartilage and that Zfhx4 deficient mice had reduced expression of matrix metallopeptidase 13 and inhibited calcification of cartilage matrices. These phenotypes were very similar to impaired chondrogenesis in Osterix deficient mice. Coimmunoprecipitation and immunofluorescence indicated a physical interaction between Zfhx4 and Osterix. Notably, Zfhx4 and Osterix double mutant mice showed more severe phenotype than Zfhx4 deficient mice. Additionally, Zfhx4 interacted with Runx2 that functions upstream of Osterix. Our findings suggest that Zfhx4 coordinates the transcriptional network of Osterix and, consequently, endochondral ossification.
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