{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:58:59Z","timestamp":1778223539981,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T00:00:00Z","timestamp":1193616000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ther Apher Dial"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> The regulation of phosphate homeostasis remains incompletely understood. Most insights into the underlying mechanisms were established by defining the molecular basis of different inherited disorders that are characterized by an abnormal regulation of phosphate homeostasis. Using this approach, three novel regulators were previously identified, namely PHEX (a phosphate\u2010regulating gene with homologies to endopeptidases on the X\u2003chromosome), fibroblast growth factor (FGF)\u201023 and UDP\u2010N\u2010acetyl\u2010\u03b1\u2010D\u2010galactosamine:polypeptide N\u2010acetylgalactosaminyltransferase\u20033 (GALNT3). Other studies had revealed heterozygous mutations in the sodium phosphate co\u2010transporter NaPi\u2010IIa as the cause of hypophosphatemia associated with hypercalciuria and osteoporosis, and homozygous or compound heterozygous mutations in NaPi\u2010IIc were shown to cause hereditary hypophosphatemic rickets with hypercalciuria. Recently, positional cloning approaches furthermore led to the identification of homozygous inactivating mutations in dentin matrix protein\u20031 (DMP1) as the cause of an autosomal recessive form of hypophosphatemia. Using different immunometric assays, intact and C\u2010terminal FGF\u201023 levels were found to be elevated in patients with oncogenic osteomalacia, and the tumors responsible for this disease showed increased expression of FGF\u201023 mRNA. Intact and C\u2010terminal FGF\u201023 levels are furthermore elevated in patients with X\u2010linked hypophosphatemia. This disorder is caused by inactivating PHEX mutations suggesting that this endopeptidase is somehow, most likely indirectly, involved in the metabolism of intact FGF\u201023. FGF\u201023 levels were also found to be elevated in some patients with ARHP indicating that the lack of DMP1 up\u2010regulates expression of this phosphaturic hormone. The concentration of C\u2010terminal FGF\u201023, but not of intact FGF\u201023, is significantly elevated in two forms of tumoral calcinosis (TC). One form of TC is caused by homozygous inactivating GALNT3 mutations implying that the encoded enzyme, which is involved in the initiation of O\u2010glycosylation, is important for preventing cleavage of FGF\u201023 into biologically inactive fragments. The second form of tumoral calcinosis is caused by different homozygous FGF\u201023 mutations that affect conserved serine residues that may undergo O\u2010glycosylation by GALNT3; the lack of this post\u2010translational modification leads to an abnormal processing of FGF\u201023 and increased secretion of C\u2010terminal fragments. It remains unknown whether and how the different phosphate\u2010regulating proteins interact with each other and it appears very likely that additional proteins are involved in this process. It also remains unclear whether the dramatically elevated FGF\u201023 levels in patients with different stages of chronic kidney disease affect bone metabolism, particularly the mineralization of newly formed osteoid.<\/jats:p>","DOI":"10.1111\/j.1744-9987.2007.00513.x","type":"journal-article","created":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T22:08:57Z","timestamp":1193695737000},"source":"Crossref","is-referenced-by-count":28,"title":["Novel Regulators of Phosphate Homeostasis and Bone Metabolism"],"prefix":"10.1111","volume":"11","author":[{"given":"Harald","family":"J\u00fcppner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,10,29]]},"reference":[{"key":"e_1_2_9_2_2","first-page":"920","volume-title":"Endocrinology","author":"Potts JT","year":"1996"},{"key":"e_1_2_9_3_2","first-page":"1377","volume-title":"Endocrinology","author":"J\u00fcppner 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