{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:40:47Z","timestamp":1790422847623,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T00:00:00Z","timestamp":1644105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation - Flanders","doi-asserted-by":"publisher","award":["11F2121N"],"award-info":[{"award-number":["11F2121N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Soci\u00e9t\u00e9 Fran\u00e7aise de N\u00e9phrologie, Dialyse et Transplantation","award":["IRCT-Dialyse 2020"],"award-info":[{"award-number":["IRCT-Dialyse 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pseudoxanthoma elasticum (PXE) is an intractable Mendelian disease characterized by ectopic calcification in skin, eyes and blood vessels. Recently, increased activation of the DNA damage response (DDR) was shown to be involved in PXE pathogenesis, while the DDR\/PARP1 inhibitor minocycline was found to attenuate aberrant mineralization in PXE cells and zebrafish. In this proof-of-concept study, we evaluated the anticalcifying properties of minocycline in Abcc6\u2212\/\u2212 mice, an established mammalian PXE model. Abcc6\u2212\/\u2212 mice received oral minocycline supplementation (40 mg\/kg\/day) from 12 to 36 weeks of age and were compared to untreated Abcc6\u2212\/\u2212 and Abcc6+\/+ siblings. Ectopic calcification was evaluated using X-ray microtomography with three-dimensional reconstruction of calcium deposits in muzzle skin and Yasue\u2019s calcium staining. Immunohistochemistry for the key DDR marker H2AX was also performed. Following minocycline treatment, ectopic calcification in Abcc6\u2212\/\u2212 mice was significantly reduced (\u221243.4%, p &lt; 0.0001) compared to untreated Abcc6\u2212\/\u2212 littermates. H2AX immunostaining revealed activation of the DDR at sites of aberrant mineralization in untreated Abcc6\u2212\/\u2212 animals. In conclusion, we validated the anticalcifying effect of minocycline in Abcc6\u2212\/\u2212 mice for the first time. Considering its favorable safety profile in humans and low cost as a generic drug, minocycline may be a promising therapeutic compound for PXE patients.<\/jats:p>","DOI":"10.3390\/ijms23031838","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:36:47Z","timestamp":1644179807000},"page":"1838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Minocycline Counteracts Ectopic Calcification in a Murine Model of Pseudoxanthoma Elasticum: A Proof-of-Concept Study"],"prefix":"10.3390","volume":"23","author":[{"given":"Elise","family":"Bouderlique","sequence":"first","affiliation":[{"name":"UMR S 1155, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Sorbonne Universit\u00e9, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0464-0190","authenticated-orcid":false,"given":"Lukas","family":"Nollet","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"},{"name":"Ectopic Mineralization Research Group, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Letavernier","sequence":"additional","affiliation":[{"name":"UMR S 1155, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Sorbonne Universit\u00e9, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier M.","family":"Vanakker","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"},{"name":"Ectopic Mineralization Research Group, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.12998\/wjcc.v3.i7.556","article-title":"From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders","volume":"3","author":"Vanakker","year":"2015","journal-title":"World J. 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