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


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
03 11 2021
Historique:
received: 30 01 2020
accepted: 18 10 2021
entrez: 4 11 2021
pubmed: 5 11 2021
medline: 21 12 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34732852
doi: 10.1038/s42003-021-02793-9
pii: 10.1038/s42003-021-02793-9
pmc: PMC8566502
doi:

Substances chimiques

Homeodomain Proteins 0
Sp7 Transcription Factor 0
Sp7 protein, mouse 0
Zfhx4 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1258

Subventions

Organisme : Japan Society for the Promotion of Science London (JSPS London)
ID : 21H04841
Organisme : Japan Society for the Promotion of Science London (JSPS London)
ID : A16H063930
Organisme : Japan Society for the Promotion of Science London (JSPS London)
ID : T20K204750

Informations de copyright

© 2021. The Author(s).

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Auteurs

Eriko Nakamura (E)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan. enakamura@dent.osaka-u.ac.jp.

Kenji Hata (K)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Yoshifumi Takahata (Y)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Hiroshi Kurosaka (H)

Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Makoto Abe (M)

Department of Oral Anatomy and Developmental Biology, Osaka University, Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Takaya Abe (T)

Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima Minami-machi, Chuou-ku, Kobe, 650-0047, Japan.

Miho Kihara (M)

Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima Minami-machi, Chuou-ku, Kobe, 650-0047, Japan.

Toshihisa Komori (T)

Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan.

Sachi Kobayashi (S)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Tomohiko Murakami (T)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Toshihiro Inubushi (T)

Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Takashi Yamashiro (T)

Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Shiori Yamamoto (S)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Haruhiko Akiyama (H)

Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, 501-1194, Japan.

Makoto Kawaguchi (M)

Division of Diagnostic Pathology, Niigata Rosai Hospital, Japan Organization of Occupational Health and Safety, 1-7-12 Toh-un-cho, Johetsu, Niigata, 942-8502, Japan.

Nobuo Sakata (N)

Department of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan.

Riko Nishimura (R)

Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan. rikonisi@dent.osaka-u.ac.jp.

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