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Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis

Antxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia, pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation remains to be...

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Autores principales: Jiang, Qing, Qin, Xin, Yoshida, Carolina Andrea, Komori, Hisato, Yamana, Kei, Ohba, Shinsuke, Hojo, Hironori, Croix, Brad St., Kawata-Matsuura, Viviane K. S., Komori, Toshihisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178079/
https://www.ncbi.nlm.nih.gov/pubmed/32244499
http://dx.doi.org/10.3390/ijms21072425
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author Jiang, Qing
Qin, Xin
Yoshida, Carolina Andrea
Komori, Hisato
Yamana, Kei
Ohba, Shinsuke
Hojo, Hironori
Croix, Brad St.
Kawata-Matsuura, Viviane K. S.
Komori, Toshihisa
author_facet Jiang, Qing
Qin, Xin
Yoshida, Carolina Andrea
Komori, Hisato
Yamana, Kei
Ohba, Shinsuke
Hojo, Hironori
Croix, Brad St.
Kawata-Matsuura, Viviane K. S.
Komori, Toshihisa
author_sort Jiang, Qing
collection PubMed
description Antxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia, pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation remains to be clarified. Runx2 is essential for osteoblast differentiation and chondrocyte maturation and regulates chondrocyte proliferation through Ihh induction. In the search of Runx2 target genes in chondrocytes, we found that Antxr1 expression is upregulated by Runx2. Antxr1 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Antxr1(–/–) mice. However, the limbs of Antxr1(–/–) mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Antxr1 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Antxr1, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Antxr1 causes chondrocyte apoptosis accompanied by matrix mineralization.
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spelling pubmed-71780792020-04-28 Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis Jiang, Qing Qin, Xin Yoshida, Carolina Andrea Komori, Hisato Yamana, Kei Ohba, Shinsuke Hojo, Hironori Croix, Brad St. Kawata-Matsuura, Viviane K. S. Komori, Toshihisa Int J Mol Sci Article Antxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia, pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation remains to be clarified. Runx2 is essential for osteoblast differentiation and chondrocyte maturation and regulates chondrocyte proliferation through Ihh induction. In the search of Runx2 target genes in chondrocytes, we found that Antxr1 expression is upregulated by Runx2. Antxr1 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Antxr1(–/–) mice. However, the limbs of Antxr1(–/–) mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Antxr1 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Antxr1, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Antxr1 causes chondrocyte apoptosis accompanied by matrix mineralization. MDPI 2020-03-31 /pmc/articles/PMC7178079/ /pubmed/32244499 http://dx.doi.org/10.3390/ijms21072425 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiang, Qing
Qin, Xin
Yoshida, Carolina Andrea
Komori, Hisato
Yamana, Kei
Ohba, Shinsuke
Hojo, Hironori
Croix, Brad St.
Kawata-Matsuura, Viviane K. S.
Komori, Toshihisa
Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
title Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
title_full Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
title_fullStr Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
title_full_unstemmed Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
title_short Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
title_sort antxr1, which is a target of runx2, regulates chondrocyte proliferation and apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178079/
https://www.ncbi.nlm.nih.gov/pubmed/32244499
http://dx.doi.org/10.3390/ijms21072425
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