{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:19:34Z","timestamp":1791314374589,"version":"4.3.1"},"reference-count":54,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>\n                    Based on its homology to the estrogen receptor and its roles in osteoblast and chondrocyte differentiation, the orphan nuclear receptor estrogen-related receptor \u03b1 (ERR\u03b1 (ESRRA)) is an intriguing therapeutic target for osteoporosis and other bone diseases. The objective of this study was to better characterize the molecular mechanisms by which ERR\u03b1 modulates osteoblastogenesis. Experiments from multiple systems demonstrated that ERR\u03b1 modulates Wnt signaling, a crucial pathway for proper regulation of bone development. This was validated using a Wnt-luciferase reporter, where ERR\u03b1 showed co-activator-dependent (peroxisome proliferator-activated receptor gamma co-activator 1\u03b1, PGC-1\u03b1) stimulatory effects. Interestingly, knockdown of\n                    <jats:italic>ERR<\/jats:italic>\n                    <jats:italic>\u03b1<\/jats:italic>\n                    expression also enhanced WNT signaling. In combination, these data indicated that ERR\u03b1 could serve to either activate or repress Wnt signaling depending on the presence or absence of its co-activator PGC-1\u03b1. The observed Wnt pathway modulation was cell intrinsic and did not alter \u03b2-catenin nuclear translocation but was dependent on DNA binding of ERR\u03b1. We also found that expression of active ERR\u03b1 correlated with Wnt pathway effects on osteoblastic differentiation in two cell types, consistent with a role for ERR\u03b1 in modulating the Wnt pathway. In conclusion, this work identifies ERR\u03b1, in conjunction with co-activators such as PGC-1\u03b1, as a new regulator of the Wnt-signaling pathway during osteoblast differentiation, through a cell-intrinsic mechanism not affecting \u03b2-catenin nuclear translocation.\n                  <\/jats:p>","DOI":"10.1530\/jme-11-0140","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T23:21:16Z","timestamp":1329261676000},"page":"177-191","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":51,"title":["Estrogen-related receptor \u03b1 regulates osteoblast differentiation via Wnt\/\u03b2-catenin signaling"],"prefix":"10.1530","volume":"48","author":[{"given":"Kathryn L","family":"Auld","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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