{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:34:55Z","timestamp":1773916495982,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council, Taiwan","doi-asserted-by":"crossref","award":["NSC 98-2311-B-415-001-MY3"],"award-info":[{"award-number":["NSC 98-2311-B-415-001-MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council, Taiwan","doi-asserted-by":"crossref","award":["NSC 101-2311-B-415-001"],"award-info":[{"award-number":["NSC 101-2311-B-415-001"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Estrogen is a crucial hormone for osteoclast inhibition and for preventing osteoporosis. However, the hormone's role in osteoblast growth and differentiation remains unclear. The complexity of estrogen's role in guiding osteoblast behavior arises partly from crosstalk with other signaling pathways, including Wnt signaling. In this study, we show that the Wnt agonist, LiCl, induced <jats:italic>Fhl1<\/jats:italic> gene expression, which substantially enhanced osteoblast differentiation. Staining with alizarin red revealed that MC3T3\u2010E1 mineralization was enhanced by overexpression of <jats:italic>Fhl1<\/jats:italic>. In addition, <jats:italic>Fhl1<\/jats:italic> promoted the expression of the osteogenic markers, <jats:italic>Runt\u2010related transcription factor 2<\/jats:italic> (Runx2), osteocalcin (<jats:italic>OCN<\/jats:italic>), and <jats:italic>osteopontin<\/jats:italic> (<jats:italic>OPN<\/jats:italic>), whereas MC3T3\u2010E1 cells with gene knockdown of <jats:italic>Fhl1<\/jats:italic> exhibited limited mineralization and expression of Runx2, <jats:italic>OCN<\/jats:italic>, and <jats:italic>OPN<\/jats:italic>. We further demonstrate evidences from quantitative reverse transcription real\u2010time polymerase chain reaction and reporter assay that <jats:italic>Fhl1<\/jats:italic> expression was synergistically stimulated by estrogen (E2) and LiCl, but reduced by the estrogen\u2010receptor inhibitor fulvestrant (ICI 182,780). However, estrogen could not enhance osteogenesis while <jats:italic>Fhl1<\/jats:italic> expression was knocked down. Because estrogen and Wnt signaling frequently interact in developmental processes, we propose that Fhl1 can be an acting molecule mediating both signaling pathways during osteogenesis. J. Cell. Biochem. 116: 1419\u20131430, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25102","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T01:14:40Z","timestamp":1423790080000},"page":"1419-1430","source":"Crossref","is-referenced-by-count":22,"title":["Estrogen Enhances Activity of Wnt Signaling During Osteogenesis by Inducing Fhl1 Expression"],"prefix":"10.1002","volume":"116","author":[{"given":"Shao\u2010Min","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Bio\u2010Agricultural Sciences National Chiayi University Chiayi 60004 Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan\u2010Hsin","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Bio\u2010Agricultural Sciences National Chiayi University Chiayi 60004 Taiwan, 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