{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:54Z","timestamp":1784557254299,"version":"3.55.0"},"reference-count":66,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>\n                    The type I transmembrane protein \u03b1Klotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts\/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exogenously added sKL on osteoblasts and bone using Klotho-deficient (\n                    <jats:italic>kl\/kl<\/jats:italic>\n                    ) mice and cell and organ cultures. sKL induced FGF23 signaling in bone and exacerbated the hypomineralization without exacerbating the hyperphosphatemia, hypercalcemia and hypervitaminosis D in\n                    <jats:italic>kl\/kl<\/jats:italic>\n                    mice. The same effects were seen in rodent bone models\n                    <jats:italic>in vitro<\/jats:italic>\n                    , in which we also detected formation of a sKL complex with FGF23-FGFR and decreased\n                    <jats:italic>Phex<\/jats:italic>\n                    (gene responsible for X-linked hypophosphatemic rickets (XLH)\/osteomalacia) expression. Further, sKL-FGF23-dependent hypomineralization\n                    <jats:italic>in vitro<\/jats:italic>\n                    was rescued by soluble PHEX. These data suggest that exogenously added sKL directly participates in FGF23 signaling in bone and that PHEX is a downstream effector of the sKL-FGF23-FGFR axis in bone.\n                  <\/jats:p>","DOI":"10.1530\/joe-17-0683","type":"journal-article","created":{"date-parts":[[2018,4,9]],"date-time":"2018-04-09T07:20:08Z","timestamp":1523258408000},"page":"285-300","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":9,"title":["Soluble Klotho causes hypomineralization in Klotho-deficient mice"],"prefix":"10.1530","volume":"237","author":[{"given":"Tomoko","family":"Minamizaki","sequence":"first","affiliation":[{"name":"1Department of Calcified Tissue Biology, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Konishi","sequence":"additional","affiliation":[{"name":"1Department of Calcified Tissue Biology, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"},{"name":"2Department of Pediatric Dentistry, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Sakurai","sequence":"additional","affiliation":[{"name":"1Department of Calcified Tissue Biology, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"},{"name":"2Department of Pediatric Dentistry, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"1Department of Calcified Tissue Biology, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E","family":"Aubin","sequence":"additional","affiliation":[{"name":"3Department of Molecular Genetics, University of Toronto, 1 King\u2019s College Circle, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Kozai","sequence":"additional","affiliation":[{"name":"2Department of Pediatric Dentistry, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Yoshiko","sequence":"additional","affiliation":[{"name":"1Department of Calcified Tissue Biology, School of Dentistry, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref521","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cca.2009.06.011","article-title":"KLOTHO gene polymorphisms G-395A and C1818T are associated with lipid and glucose metabolism, bone mineral density and systolic blood pressure in Japanese healthy subjects","volume":"406","year":"2009","journal-title":"Clinica Chimica Acta"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jsbmb.2006.12.054","article-title":"1,25-Dihydroxyvitamin D3\/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism","volume":"103","year":"2007","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1126\/science.1143578","article-title":"Augmented Wnt signaling in a mammalian model of accelerated aging","volume":"317","year":"2007","journal-title":"Science"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.clinbiochem.2013.05.046","article-title":"Soluble serum Klotho levels in healthy subjects. 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