{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:59:24Z","timestamp":1790949564939,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,2,24]],"date-time":"2012-02-24T00:00:00Z","timestamp":1330041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>PHosphate\u2010regulating gene with homology to Endopeptidase on the X chromosome (PHEX) has been identified as the gene mutated in X\u2010linked hypophosphatemia (XLH) syndrome, the most prevalent form of rickets in humans. The predominant expression of <jats:italic>PHEX<\/jats:italic> in bones and teeth, and the defective mineralization of these tissues in XLH patients indicate that PHEX is an important regulator of mineralization. Parathyroid hormone (PTH) and PTH\u2010related protein (PTHrP) are known to regulate the expression of numerous genes in osteoblastic cells through activation of the protein kinase A pathway, including repression of <jats:italic>PHEX<\/jats:italic>. PTH also activates the transcriptional repressor E4BP4 through the same pathway, suggesting that PTH or PTHrP\u2010mediated repression of <jats:italic>PHEX<\/jats:italic> expression could involve E4BP4. To evaluate this possibility, we treated UMR\u2010106 osteoblastic cells with PTHrP(1\u201034), and used RT\u2010PCR and immunoblotting to analyze <jats:italic>PHEX<\/jats:italic> and <jats:italic>E4BP4<\/jats:italic> expression. <jats:italic>E4BP4<\/jats:italic> mRNA and protein levels were rapidly increased in cells treated with PTHrP(1\u201034), with a concomitant decrease in <jats:italic>PHEX<\/jats:italic> expression. This downregulation of <jats:italic>PHEX<\/jats:italic> could be reproduced by overexpression of E4BP4. Moreover, PTHrP(1\u201034)\u2010mediated <jats:italic>PHEX<\/jats:italic> repression was blocked when cells were transfected with a siRNA targeting <jats:italic>E4BP4<\/jats:italic> mRNA. Finally, DNA pull\u2010down and luciferase assays showed that two E4BP4 response elements located in PHEX promoter were functional. These results underline the important role of E4BP4 in osteoblastic cells and further define the repression mechanism of PHEX gene by PTHrP(1\u201034). J. Cell. Physiol. 227: 2378\u20132387, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22973","type":"journal-article","created":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T14:02:37Z","timestamp":1312812157000},"page":"2378-2387","source":"Crossref","is-referenced-by-count":5,"title":["PTHrP(1\u201034)\u2010mediated repression of the PHEX gene in osteoblastic cells involves the transcriptional repressor 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