{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:49:58Z","timestamp":1791805798585,"version":"4.3.4"},"reference-count":127,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T00:00:00Z","timestamp":1414540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","award":["#994\/10, #1018\/13"],"award-info":[{"award-number":["#994\/10, #1018\/13"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Body phosphate homeostasis is regulated by a hormonal counter\u2010balanced intestine\u2010bone\u2010kidney axis. The major systemic hormones involved in this axis are parathyroid hormone (PTH), 1,25\u2010dihydroxyvitamin\u2010D, and fibroblast growth factor\u201023 (FGF23). FGF23, produced almost exclusively by the osteocytes, is a phosphaturic hormone that plays a major role in regulation of the bone remodeling process. Remodeling composite components, bone mineralization and resorption cycles create a continuous influx\u2010efflux loop of the inorganic phosphate (Pi) through the skeleton. This \u201cbone Pi loop,\u201d which is formed, is controlled by local and systemic factors according to phosphate homeostasis demands. Although FGF23 systemic actions in the kidney, and for the production of PTH and 1,25\u2010dihydroxyvitamin\u2010D are well established, its direct involvement in bone metabolism is currently poorly understood. This review presents the latest available evidence suggesting two aspects of FGF23 bone local activity: (<jats:italic>a<\/jats:italic>) Regulation of FGF23 production by both local and systemic factors. The suggested local factors include extracellular levels of Pi and pyrophosphate (PPi), (the Pi\/PPi ratio), and another osteocyte\u2010derived protein, sclerostin. In addition, 1,25\u2010dihydroxyvitamin\u2010D, synthesized locally by bone cells, may contribute to regulation of FGF23 production. The systemic control is achieved via PTH and 1,25\u2010dihydroxyvitamin\u2010D endocrine functions. (<jats:italic>b<\/jats:italic>) FGF23 acts as a local agent, directly affecting bone mineralization. We support the assumption that under balanced physiological conditions, sclerostin, by para\u2010 autocrine signaling, upregulates FGF23 production by the osteocyte. FGF23, in turn, acts as a mineralization inhibitor, by stimulating the generation of the major mineralization antagonist\u2014PPi. \u00a9 2014 BioFactors, 40(6):555\u2013568, 2014<\/jats:p>","DOI":"10.1002\/biof.1186","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T07:15:24Z","timestamp":1414566924000},"page":"555-568","source":"Crossref","is-referenced-by-count":37,"title":["Bone mineralization is regulated by signaling cross talk between molecular factors of local and systemic origin: The role of fibroblast growth factor 23"],"prefix":"10.1002","volume":"40","author":[{"given":"Rony","family":"Sapir\u2010Koren","sequence":"first","affiliation":[{"name":"Human Population Biology Research Unit Department of Anatomy and Anthropology Sackler Faculty of Medicine, Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Livshits","sequence":"additional","affiliation":[{"name":"Human Population Biology Research Unit Department of Anatomy and Anthropology Sackler Faculty of Medicine, Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90538.2008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0527-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-010-9153-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.433"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.06.014"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.01.017"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.02.027"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902006107"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419081"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-011-9199-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1138\/20110516"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00243.2005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2006.12.054"},{"key":"e_1_2_9_15_1","first-page":"4003","article-title":"The parathyroid is a target organ for FGF23 in rats","volume":"117","author":"Ben Dov I. Z.","year":"2007","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0267"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e32832c2264"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00360.2010"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500457200"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502267200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.070234"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.041087"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1402.018"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040128"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.03.021"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2309-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.4538"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.01.046"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650040407"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.2.165"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00008.2006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1905"},{"key":"e_1_2_9_33_1","first-page":"722","article-title":"Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X\u2010linked hypophosphatemia","volume":"118","author":"Yuan B.","year":"2008","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/81664"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-011-0340-2"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.101545198"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5084"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(00)00334-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/522240"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1850"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.06.026"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1217817"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002708"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.07.009"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1402218111"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi034"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.9.5372"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1994.267.5.F900"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2004.09.007"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650070213"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1998.275.4.E700"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00396.2007"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0113"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050212"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1766"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.12.009"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.11.033"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-177816"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093840"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9774-y"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v22.i1.50"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.07.037"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007010068"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050815"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2014.38"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097326"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.478"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.107"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011101006"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221255110"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701116200"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2011.01.004"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0777"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0021"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060507"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.03.002"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00502.2004"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-007-0779-3"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140021997"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304470200"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2012.09.029"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-005-5304-3"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.010"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.006"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24312"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9831-6"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1491"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.5.537"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.2.91"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1207188109"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg599"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.10.025"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090411"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-2808-0"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.345"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06057"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006070783"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.06.025"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0472"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513516344"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.02.024"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.024"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0334"},{"key":"e_1_2_9_104_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jsbmb.2013.09.016","article-title":"Analysis of vitamin D metabolism gene expression in human bone: evidence for autocrine control of bone remodeling","volume":"144","author":"Ormsby R. T.","year":"2013","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05315"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-114397"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.24"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0085"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/36285"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112766"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2012.753879"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183727"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2008.00859.x"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90539.2008"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-123992"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9795-6"},{"key":"e_1_2_9_117_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000154"},{"key":"e_1_2_9_118_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080220"},{"key":"e_1_2_9_119_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-011-9501-5"},{"key":"e_1_2_9_120_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032177"},{"key":"e_1_2_9_121_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000414"},{"key":"e_1_2_9_122_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.327"},{"key":"e_1_2_9_123_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.271"},{"key":"e_1_2_9_124_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019595"},{"key":"e_1_2_9_125_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.07.014"},{"key":"e_1_2_9_126_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1630"},{"key":"e_1_2_9_127_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61405"},{"key":"e_1_2_9_128_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72829"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbiof.1186","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbiof.1186","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.1186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:13:51Z","timestamp":1696601631000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.1186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,29]]},"references-count":127,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1002\/biof.1186"],"URL":"https:\/\/doi.org\/10.1002\/biof.1186","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,29]]}}}