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

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...

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Autores principales: Nakamura, Eriko, Hata, Kenji, Takahata, Yoshifumi, Kurosaka, Hiroshi, Abe, Makoto, Abe, Takaya, Kihara, Miho, Komori, Toshihisa, Kobayashi, Sachi, Murakami, Tomohiko, Inubushi, Toshihiro, Yamashiro, Takashi, Yamamoto, Shiori, Akiyama, Haruhiko, Kawaguchi, Makoto, Sakata, Nobuo, Nishimura, Riko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566502/
https://www.ncbi.nlm.nih.gov/pubmed/34732852
http://dx.doi.org/10.1038/s42003-021-02793-9
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author Nakamura, Eriko
Hata, Kenji
Takahata, Yoshifumi
Kurosaka, Hiroshi
Abe, Makoto
Abe, Takaya
Kihara, Miho
Komori, Toshihisa
Kobayashi, Sachi
Murakami, Tomohiko
Inubushi, Toshihiro
Yamashiro, Takashi
Yamamoto, Shiori
Akiyama, Haruhiko
Kawaguchi, Makoto
Sakata, Nobuo
Nishimura, Riko
author_facet Nakamura, Eriko
Hata, Kenji
Takahata, Yoshifumi
Kurosaka, Hiroshi
Abe, Makoto
Abe, Takaya
Kihara, Miho
Komori, Toshihisa
Kobayashi, Sachi
Murakami, Tomohiko
Inubushi, Toshihiro
Yamashiro, Takashi
Yamamoto, Shiori
Akiyama, Haruhiko
Kawaguchi, Makoto
Sakata, Nobuo
Nishimura, Riko
author_sort Nakamura, Eriko
collection PubMed
description 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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spelling pubmed-85665022021-11-19 Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice Nakamura, Eriko Hata, Kenji Takahata, Yoshifumi Kurosaka, Hiroshi Abe, Makoto Abe, Takaya Kihara, Miho Komori, Toshihisa Kobayashi, Sachi Murakami, Tomohiko Inubushi, Toshihiro Yamashiro, Takashi Yamamoto, Shiori Akiyama, Haruhiko Kawaguchi, Makoto Sakata, Nobuo Nishimura, Riko Commun Biol Article 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. Nature Publishing Group UK 2021-11-03 /pmc/articles/PMC8566502/ /pubmed/34732852 http://dx.doi.org/10.1038/s42003-021-02793-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nakamura, Eriko
Hata, Kenji
Takahata, Yoshifumi
Kurosaka, Hiroshi
Abe, Makoto
Abe, Takaya
Kihara, Miho
Komori, Toshihisa
Kobayashi, Sachi
Murakami, Tomohiko
Inubushi, Toshihiro
Yamashiro, Takashi
Yamamoto, Shiori
Akiyama, Haruhiko
Kawaguchi, Makoto
Sakata, Nobuo
Nishimura, Riko
Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
title Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
title_full Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
title_fullStr Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
title_full_unstemmed Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
title_short Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
title_sort zfhx4 regulates endochondral ossification as the transcriptional platform of osterix in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566502/
https://www.ncbi.nlm.nih.gov/pubmed/34732852
http://dx.doi.org/10.1038/s42003-021-02793-9
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