{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:54:29Z","timestamp":1790751269691,"version":"4.1.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU-01"],"award-info":[{"award-number":["ANR-10-IAHU-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DGE20111123012, FDM20140731354"],"award-info":[{"award-number":["DGE20111123012, FDM20140731354"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>X-linked hypophosphatemia (XLH) is a skeletal disease caused by inactivating mutations in the PHEX gene. Mutated or absent PHEX protein\/enzyme leads to a decreased serum phosphate level, which cause mineralization defects in the skeleton and teeth (osteomalacia\/odontomalacia). It is not yet altogether clear whether these manifestations are caused solely by insufficient circulating phosphate availability for mineralization or also by a direct, local intrinsic effect caused by impaired PHEX activity. Here, we evaluated the local role of PHEX in a 3-dimensional model of extracellular matrix (ECM) mineralization. Dense collagen hydrogels were seeded either with human dental pulp cells from patients with characterized PHEX mutations or with sex- and age-matched healthy controls and cultured up to 24 d using osteogenic medium with standard phosphate concentration. Calcium quantification, micro\u2013computed tomography, and histology with von Kossa staining for mineral showed significantly lower mineralization in XLH cell-seeded scaffolds, using nonparametric statistical tests. While apatitic mineralization was observed along collagen fibrils by electron microscopy in both groups, Raman microspectrometry indicated that XLH cells harboring the PHEX mutation produced less mineralized scaffolds having impaired mineral quality with less carbonate substitution and lower crystallinity. In the XLH cultures, immunoblotting revealed more abundant osteopontin (OPN), dentin matrix protein 1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE) than controls, as well as the presence of fragments of these proteins not found in controls, suggesting a role for PHEX in SIBLING protein degradation. Immunohistochemistry revealed altered OPN and DMP1 associated with an increased alkaline phosphatase staining in the XLH cultures. These results are consistent with impaired PHEX activity having local ECM effects in XLH. Future treatments for XLH should target both systemic and local manifestations.<\/jats:p>","DOI":"10.1177\/0022034517728497","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T15:34:56Z","timestamp":1504798496000},"page":"184-191","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["Defective Mineralization in X-Linked Hypophosphatemia Dental Pulp Cell Cultures"],"prefix":"10.1177","volume":"97","author":[{"given":"B.R.","family":"Coyac","sequence":"first","affiliation":[{"name":"EA 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Dental School University Paris Descartes Sorbonne Paris Cit\u00e9, and Life imaging Platform (PIV), Montrouge, France"},{"name":"Department of Periodontology, U.F.R. of Odontology, Rothschild Hospital, AP-HP, Paris Diderot University, Paris, France"},{"name":"Faculty of Dentistry, Division of Biomedical Sciences, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Hoac","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Division of Biomedical Sciences, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Chafey","sequence":"additional","affiliation":[{"name":"INSERM U1016, Institut Cochin and Proteomic core facility of University Paris Descartes (3P5) Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Falgayrac","sequence":"additional","affiliation":[{"name":"Lille University, University of Littoral C\u00f4te d\u2019Opale, EA 4490\u2013PMOI\u2013Pathophysiology of Inflammatory Bone Diseases, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Slimani","sequence":"additional","affiliation":[{"name":"EA 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Dental School University Paris Descartes Sorbonne Paris Cit\u00e9, and Life imaging Platform (PIV), Montrouge, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.S.","family":"Rowe","sequence":"additional","affiliation":[{"name":"The Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Penel","sequence":"additional","affiliation":[{"name":"Lille University, University of Littoral C\u00f4te d\u2019Opale, EA 4490\u2013PMOI\u2013Pathophysiology of Inflammatory Bone Diseases, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Linglart","sequence":"additional","affiliation":[{"name":"APHP, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Plateforme of Expertise Paris Sud for Rare Disesdes, fili\u00e8re OSCAR, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM U1169, University Paris Sud Paris-Saclay, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.D.","family":"McKee","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Division of Biomedical Sciences, McGill University, Montreal, QC, Canada"},{"name":"Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Chaussain","sequence":"additional","affiliation":[{"name":"EA 2496 Laboratory Orofacial Pathologies, Imaging and Biotherapies, Dental School University Paris Descartes Sorbonne Paris Cit\u00e9, and Life imaging Platform (PIV), Montrouge, France"},{"name":"APHP, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Plateforme of Expertise Paris Sud for Rare Disesdes, fili\u00e8re OSCAR, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Odontology, Bretonneau Hospital PNVS, 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