{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:03:46Z","timestamp":1791277426848,"version":"4.1.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"DOI":"10.1371\/journal.pbio.1002427","type":"journal-article","created":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T17:36:58Z","timestamp":1459532218000},"page":"e1002427","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":128,"title":["Excessive Osteocytic Fgf23 Secretion Contributes to Pyrophosphate Accumulation and Mineralization Defect in Hyp Mice"],"prefix":"10.1371","volume":"14","author":[{"given":"Sathish K.","family":"Murali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Andrukhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica L.","family":"Clinkenbeard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold G.","family":"Erben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/ng1095-130","article-title":"A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets","volume":"11","author":"F Francis","year":"1995","journal-title":"Nat Genet"},{"key":"ref2","first-page":"790","article-title":"Mutational analysis of the PEX gene in patients with X-linked hypophosphatemic rickets","volume":"60","author":"IA Holm","year":"1997","journal-title":"Am J Hum Genet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/hmg\/6.4.539","article-title":"Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)","volume":"6","author":"PS Rowe","year":"1997","journal-title":"Hum Mol Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1172\/JCI119276","article-title":"Pex\/PEX tissue distribution and evidence for a deletion in the 3&apos; region of the Pex gene in X-linked hypophosphatemic mice","volume":"99","author":"L Beck","year":"1997","journal-title":"J Clin Invest"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1006\/geno.1996.0421","article-title":"cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone","volume":"36","author":"L Du","year":"1996","journal-title":"Genomics"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/hmg\/6.2.165","article-title":"Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia","volume":"6","author":"TM Strom","year":"1997","journal-title":"Hum Mol Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1177\/002215549804600405","article-title":"Pex mRNA is localized in developing mouse osteoblasts and odontoblasts","volume":"46","author":"AF Ruchon","year":"1998","journal-title":"J Histochem Cytochem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1359\/JBMR.050212","article-title":"Overexpression of human PHEX under the human beta-actin promoter does not fully rescue the Hyp mouse phenotype","volume":"20","author":"RG Erben","year":"2005","journal-title":"J Bone Miner Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/jbmr.275","article-title":"Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice","volume":"26","author":"Y Aono","year":"2011","journal-title":"J Bone Miner Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/ndt\/14.2.333","article-title":"X-linked hypophosphataemia: a homologous disorder in humans and mice","volume":"14","author":"HS Tenenhouse","year":"1999","journal-title":"Nephrol Dial Transplant"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1056\/NEJMoa020881","article-title":"Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia","volume":"348","author":"KB Jonsson","year":"2003","journal-title":"N Engl J Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1074\/jbc.M408903200","article-title":"Circulating FGF-23 is regulated by 1alpha,25-dihydroxyvitamin D3 and phosphorus in vivo","volume":"280","author":"H Saito","year":"2005","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/emmm.201303716","article-title":"FGF23 regulates renal sodium handling and blood pressure","volume":"6","author":"O Andrukhova","year":"2014","journal-title":"EMBO Mol Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1359\/JBMR.0301264","article-title":"FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis","volume":"19","author":"T Shimada","year":"2004","journal-title":"J Bone Miner Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1359\/jbmr.090509","article-title":"Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets\/osteomalacia","volume":"24","author":"Y Aono","year":"2009","journal-title":"J Bone Miner Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"I Urakawa","year":"2006","journal-title":"Nature"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"M Kuro-o","year":"1997","journal-title":"Nature"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1677\/joe.1.05989","article-title":"Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets","volume":"183","author":"D Bresler","year":"2004","journal-title":"J Endocrinol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1210\/en.2007-1205","article-title":"Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP","volume":"149","author":"A Martin","year":"2008","journal-title":"Endocrinology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1749-6632.1995.tb44629.x","article-title":"Osteopontin and the bone remodeling sequence. Colloidal-gold immunocytochemistry of an interfacial extracellular matrix protein","volume":"760","author":"MD McKee","year":"1995","journal-title":"Ann N Y Acad Sci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/jbmr.1766","article-title":"Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia","volume":"28","author":"NM Barros","year":"2013","journal-title":"J Bone Miner Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng1905","article-title":"Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism","volume":"38","author":"JQ Feng","year":"2006","journal-title":"Nat Genet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e104154","DOI":"10.1371\/journal.pone.0104154","article-title":"Osteocyte-specific deletion of Fgfr1 suppresses FGF23","volume":"9","author":"Z Xiao","year":"2014","journal-title":"PLoS ONE"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1002\/jbmr.1810","article-title":"Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets","volume":"28","author":"S Wohrle","year":"2013","journal-title":"J Bone Miner Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/jbmr.544","article-title":"A Phex mutation in a murine model of X-linked hypophosphatemia alters phosphate responsiveness of bone cells","volume":"27","author":"S Ichikawa","year":"2012","journal-title":"J Bone Miner Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1073\/pnas.101545198","article-title":"Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia","volume":"98","author":"T Shimada","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.1210\/en.2004-0233","article-title":"Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders","volume":"145","author":"X Bai","year":"2004","journal-title":"Endocrinology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.matbio.2004.09.007","article-title":"Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice","volume":"23","author":"D Sitara","year":"2004","journal-title":"Matrix Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"E38","DOI":"10.1152\/ajpendo.00008.2006","article-title":"Pathogenic role of Fgf23 in Hyp mice","volume":"291","author":"S Liu","year":"2006","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref30","first-page":"E700","article-title":"Intrinsic mineralization defect in Hyp mouse osteoblasts","volume":"275","author":"ZS Xiao","year":"1998","journal-title":"Am J Physiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/jbmr.5650070508","article-title":"Effect of dietary phosphate deprivation and supplementation of recipient mice on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice","volume":"7","author":"B Ecarot","year":"1992","journal-title":"J Bone Miner Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"E1636","DOI":"10.1152\/ajpendo.00396.2007","article-title":"Distinct roles for intrinsic osteocyte abnormalities and systemic factors in regulation of FGF23 and bone mineralization in Hyp mice","volume":"293","author":"S Liu","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jbmr.2606","article-title":"FGF23 regulates bone mineralization in a 1,25(OH)2D3 and Klotho-independent manner","volume":"31","author":"SK Murali","year":"2016","journal-title":"J Bone Miner Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1172\/JCI106589","article-title":"Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone","volume":"50","author":"RG Russell","year":"1971","journal-title":"J Clin Invest"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1172\/JCI45890","article-title":"Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization","volume":"122","author":"L Lieben","year":"2012","journal-title":"J Clin Invest"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"15872","DOI":"10.1074\/jbc.M701116200","article-title":"Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity","volume":"282","author":"WN Addison","year":"2007","journal-title":"J Biol Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1359\/jbmr.060515","article-title":"Mineral formation in joints caused by complete or joint-specific loss of ANK function","volume":"21","author":"KA Gurley","year":"2006","journal-title":"J Bone Miner Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0002-9440(10)63208-7","article-title":"Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders","volume":"164","author":"D Harmey","year":"2004","journal-title":"Am J Pathol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e93840","DOI":"10.1371\/journal.pone.0093840","article-title":"Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice","volume":"9","author":"K Miyagawa","year":"2014","journal-title":"PLoS ONE"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/03008209609029169","article-title":"Study of osteoblast-specific expression of one mouse osteocalcin gene: characterization of the factor binding to OSE2","volume":"35","author":"P Ducy","year":"1996","journal-title":"Connect Tissue Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1096\/fj.05-4221fje","article-title":"Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation","volume":"19","author":"KE Poole","year":"2005","journal-title":"FASEB J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0169-6009(92)90707-K","article-title":"Inorganic phosphate added exogenously or released from beta-glycerophosphate initiates mineralization of osteoid nodules in vitro","volume":"17","author":"CG Bellows","year":"1992","journal-title":"Bone Miner"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.mce.2015.09.031","article-title":"Amphiregulin lacks an essential role for the bone anabolic action of parathyroid hormone","volume":"417","author":"FF Jay","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"ref44","article-title":"Conditional Deletion of Murine Fgf23: Interruption of the Normal Skeletal Responses to Phosphate Challenge and Rescue of Genetic Hypophosphatemia","author":"EL Clinkenbeard","year":"2016","journal-title":"J Bone Miner Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1359\/jbmr.080601","article-title":"MEPE-ASARM peptides control extracellular matrix mineralization by binding to hydroxyapatite: an inhibition regulated by PHEX cleavage of ASARM","volume":"23","author":"WN Addison","year":"2008","journal-title":"J Bone Miner Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1042\/bj20030287","article-title":"Human recombinant endopeptidase PHEX has a strict S1&apos; specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein","volume":"373","author":"M Campos","year":"2003","journal-title":"Biochem J"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bone.2003.10.005","article-title":"MEPE has the properties of an osteoblastic phosphatonin and minhibin","volume":"34","author":"PS Rowe","year":"2004","journal-title":"Bone"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1210\/me.2002-0113","article-title":"Partial rescue of the Hyp phenotype by osteoblast-targeted PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) expression","volume":"16","author":"X Bai","year":"2002","journal-title":"Mol Endocrinol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s00223-008-9201-y","article-title":"The PHEX transgene corrects mineralization defects in 9-month-old hypophosphatemic mice","volume":"84","author":"A Boskey","year":"2009","journal-title":"Calcif Tissue Int"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"9445","DOI":"10.1073\/pnas.142063399","article-title":"Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization","volume":"99","author":"L Hessle","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1359\/jbmr.2000.15.10.1879","article-title":"Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice","volume":"15","author":"C Wennberg","year":"2000","journal-title":"J Bone Miner Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jbmr.5650020111","article-title":"Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice","volume":"2","author":"RA Meyer Jr.","year":"1987","journal-title":"J Bone Miner Res"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1096\/fj.10-177816","article-title":"Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling","volume":"25","author":"A Martin","year":"2011","journal-title":"FASEB J"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/jbmr.5650100209","article-title":"Matrix mineralization and the differentiation of osteocyte-like cells in culture","volume":"10","author":"Y Mikuni-Takagaki","year":"1995","journal-title":"J Bone Miner Res"},{"key":"ref55","first-page":"004","article-title":"Computer-Automated Static, Dynamic and Cellular Bone Histomorphometry","volume":"Suppl 1","author":"SH Hong","year":"2012","journal-title":"J Tissue Sci Eng"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1177\/002215549704500215","article-title":"Embedding of bone samples in methylmethacrylate: an improved method suitable for bone histomorphometry, histochemistry, and immunohistochemistry","volume":"45","author":"RG Erben","year":"1997","journal-title":"J Histochem Cytochem"},{"key":"ref57","unstructured":"Schenk R. Preparation of calcified tissues for light microscopy, 1984; Methods of calcified tissue preparation."},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.4161\/cc.28401","article-title":"Partial inhibition of Cdk1 in G 2 phase overrides the SAC and decouples mitotic events","volume":"13","author":"RA McCloy","year":"2014","journal-title":"Cell Cycle"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1021\/pr070056t","article-title":"Method development of efficient protein extraction in bone tissue for proteome analysis","volume":"6","author":"X Jiang","year":"2007","journal-title":"J Proteome Res"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pbio.1002427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T12:14:03Z","timestamp":1718453643000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.1002427"}},"subtitle":[],"editor":[{"given":"Imelda","family":"Mcgonnell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,4,1]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.1002427","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,1]]}}}