{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:52:40Z","timestamp":1768513960238,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Ministry of Education, Culture, Sports, Science and Technology","award":["19K24124; 19K18946; 18K17017; 18H05283"],"award-info":[{"award-number":["19K24124; 19K18946; 18K17017; 18H05283"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013\/\u2013 mice. However, the limbs of Antxr1\u2013\/\u2013 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.<\/jats:p>","DOI":"10.3390\/ijms21072425","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis"],"prefix":"10.3390","volume":"21","author":[{"given":"Qing","family":"Jiang","sequence":"first","affiliation":[{"name":"Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Qin","sequence":"additional","affiliation":[{"name":"Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina Andrea","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6802-949X","authenticated-orcid":false,"given":"Hisato","family":"Komori","sequence":"additional","affiliation":[{"name":"Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Yamana","sequence":"additional","affiliation":[{"name":"Teijin Institute for Bio-Medical Research, Teijin Limited, Tokyo 100-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Ohba","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Hojo","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the University of Tokyo Graduate School of Engineering, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad St.","family":"Croix","sequence":"additional","affiliation":[{"name":"Tumor Angiogenesis Unit, National Cancer Institute (NCI), National Institutes of Health (NIH), Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane K. S.","family":"Kawata-Matsuura","sequence":"additional","affiliation":[{"name":"Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihisa","family":"Komori","sequence":"additional","affiliation":[{"name":"Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1126\/science.289.5482.1197","article-title":"Genes Expressed in Human Tumor Endothelium","volume":"289","author":"Croix","year":"2000","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/n35101999","article-title":"Identification of the cellular receptor for anthrax toxin","volume":"414","author":"Bradley","year":"2001","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.ajhg.2013.03.023","article-title":"Mutations in ANTXR1 Cause GAPO Syndrome","volume":"92","author":"Stranecky","year":"2013","journal-title":"Am. 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