{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:51:34Z","timestamp":1772603494087,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T00:00:00Z","timestamp":1511481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE14036"],"award-info":[{"award-number":["R01 DE14036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR068275"],"award-info":[{"award-number":["R01 AR068275"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>TIEG knockout (KO) mice exhibit a female\u2010specific osteopenic phenotype and altered expression of TIEG in humans is associated with osteoporosis. Gene expression profiling studies identified sclerostin as one of the most highly up\u2010regulated transcripts in the long bones of TIEG KO mice relative to WT littermates suggesting that TIEG may regulate SOST expression. TIEG was shown to substantially suppress SOST promoter activity and the regulatory elements through which TIEG functions were identified using promoter deletion and chromatin immunoprecipitation assays. Knockdown of TIEG in IDG\u2010SW3 osteocyte cells using shRNA and CRISPR\u2010Cas9 technology resulted in increased SOST expression and delayed mineralization, mimicking the results obtained from TIEG KO mouse bones. Given that TIEG is an estrogen regulated gene, and as changes in the hormonal milieu affect SOST expression, we performed ovariectomy (OVX) and estrogen replacement therapy (ERT) studies in WT and TIEG KO mice followed by miRNA and mRNA sequencing of cortical and trabecular compartments of femurs. SOST expression levels were considerably higher in cortical bone compared to trabecular bone. In cortical bone, SOST expression was increased following OVX only in WT mice and was suppressed following ERT in both genotypes. In contrast, SOST expression in trabecular bone was decreased following OVX and significantly increased following ERT. Interestingly, a number of miRNAs that are predicted to target sclerostin exhibited inverse expression levels in response to OVX and ERT. These data implicate important roles for TIEG and estrogen\u2010regulated miRNAs in modulating SOST expression in bone.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26211","type":"journal-article","created":{"date-parts":[[2017,10,16]],"date-time":"2017-10-16T20:00:49Z","timestamp":1508184049000},"page":"3540-3551","source":"Crossref","is-referenced-by-count":16,"title":["TIEG and estrogen modulate SOST expression in the murine skeleton"],"prefix":"10.1002","volume":"233","author":[{"given":"Malayannan","family":"Subramaniam","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin S.","family":"Pitel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth 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