{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:19:10Z","timestamp":1793697550800,"version":"4.5.1"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"13","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-152963"],"award-info":[{"award-number":["PJT-152963"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,11]]},"abstract":"<jats:p>\n                    We induced chronic kidney disease (CKD) with adenine in WT mice, mice with osteocyte-specific deletion of\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    , encoding the 25-hydroxyvitamin D 1(OH)ase [Oct-1(OH)ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ], and mice with global deletion of\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    [global-1\u03b1(OH)ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ]; we then compared extraskeletal calcification. After adenine treatment, mice displayed increased blood urea nitrogen, decreased serum 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D, and severe hyperparathyroidism. Skeletal expression of\n                    <jats:italic>Cyp27b1<\/jats:italic>\n                    and of sclerostin and serum sclerostin all increased in WT mice but not in Oct-1\u03b1(OH)ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice or global-1\u03b1(OH)ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice. In contrast, skeletal expression of BMP2 and serum BMP2 rose in the Oct-1\u03b1(OH\n                    <jats:italic>)<\/jats:italic>\n                    ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice and in the global-1\u03b1(OH)ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice. Extraskeletal calcification occurred in muscle and blood vessels of mice with CKD and was highest in Oct-1\u03b1(OH)ase\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice. In vitro, recombinant sclerostin (100 ng\/mL) significantly suppressed BMP2-induced osteoblastic transdifferentiation of vascular smooth muscle A7r5 cells and diminished BMP2-induced mineralization. Our study provides evidence that local osteocytic production of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D stimulates sclerostin and inhibits BMP2 production in murine CKD, thus mitigating osteoblastic transdifferentiation and mineralization of soft tissues. Increased osteocytic 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D production, triggered by renal malfunction, may represent a \u201cprimary defensive response\u201d to protect the organism from ectopic calcification by increasing sclerostin and suppressing BMP2 production.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.126467","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T11:02:24Z","timestamp":1562756544000},"source":"Crossref","is-referenced-by-count":37,"title":["Vitamin D\u2013regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification"],"prefix":"10.1172","volume":"4","author":[{"given":"Loan","family":"Nguyen-Yamamoto","sequence":"first","affiliation":[{"name":"Department of Medicine, McGill University and McGill University Health Centre, Montreal, Quebec, 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