{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:35:49Z","timestamp":1793730949834,"version":"4.6.1"},"reference-count":61,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T00:00:00Z","timestamp":1303257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Fibroblastic growth factor 23 (FGF23) is a circulating phosphaturic hormone. Inactivating mutations of the endopeptidase PHEX or the SIBLING protein DMP1 result in equivalent intrinsic bone mineralization defects and increased\n                      <jats:italic>Fgf23<\/jats:italic>\n                      expression in osteocytes. The mechanisms whereby PHEX and DMP1 regulate\n                      <jats:italic>Fgf23<\/jats:italic>\n                      expression are unknown. We examined the possibility that PHEX and DMP1 regulate\n                      <jats:italic>Fgf23<\/jats:italic>\n                      through a common pathway by analyzing the phenotype of compound Phex and Dmp1 mutant mice (Hyp\/Dmp1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      ). Compared to single\u2010mutant littermates, compound\u2010mutant Hyp\/Dmp1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      mice displayed nonadditive elevations of serum FGF23 (1912 \u00b1 183, 1715 \u00b1 178, and 1799 \u00b1 181 pg\/ml), hypophosphatemia (P\n                      <jats:sub>i<\/jats:sub>\n                      : 6.0 \u00b1 0.3, 5.8 \u00b1 0.2, and 5.4 \u00b10.1 mg\/dl), and severity of rickets\/osteomalacia (bone mineral density: \u201336, \u201336, and \u201330%). Microarray analysis of long bones identified gene expression profiles implicating common activation of the FGFR pathway in all the mutant groups. Furthermore, inhibiting FGFR signaling using SU5402 in Hyp\u2010 and Dmp1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      \u2010derived bone marrow stromal cells prevented the increase in\n                      <jats:italic>Fgf23<\/jats:italic>\n                      mRNA expression (129\u2010 and 124\u2010fold increase in Hyp and Dmp1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      <jats:italic>vs.<\/jats:italic>\n                      1.3\u2010fold in Hyp+SU5402 and 2.5\u2010fold in Dmp1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      +SU5402,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). For all analyses, samples collected from nonmutant wild\u2010type littermates served as controls. These findings indicate that PHEX and DMP1 control a common pathway regulating bone mineralization and FGF23 production, the latter involving activation of the FGFR signaling in osteocytes.\u2014Martin, A., Liu, S., David, V., Li, H., Karydis, A., Feng, J. Q., Quarles, L. D. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor\n                      <jats:italic>Fgf23<\/jats:italic>\n                      expression in osteocytes through a common pathway.\n                      <jats:italic>FASEB J.<\/jats:italic>\n                      25, 2551\u20132562 (2011).\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1096\/fj.10-177816","type":"journal-article","created":{"date-parts":[[2011,4,21]],"date-time":"2011-04-21T20:14:22Z","timestamp":1303416862000},"page":"2551-2562","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":241,"title":["Bone proteins PHEX and DMP1 regulate fibroblastic growth factor\n                    <i>Fgf23<\/i>\n                    expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling"],"prefix":"10.1096","volume":"25","author":[{"given":"Aline","family":"Martin","sequence":"first","affiliation":[{"name":"University of Tennessee Health Science Center Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiguang","family":"Liu","sequence":"additional","affiliation":[{"name":"Genzyme Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"David","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Karydis","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Q.","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Baylor College of Dentistry Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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