{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:45:34Z","timestamp":1773056734144,"version":"3.50.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Vascular calcification which refers to ectopic mineralization in vascular cells is associated with several conditions, such as chronic kidney disease, atherosclerosis, and diabetes mellitus. Estrogen-related receptor (ERR)\u03b3 is a member of the orphan nuclear receptor superfamily, which plays diverse roles in regulating homeostatic and metabolic processes. However, the role of ERR\u03b3 in vascular calcification has not been investigated to date. The aim of the present study was to examine the role of ERR\u03b3 in vascular calcification.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Vascular calcification was induced by treating rat aortic vascular smooth muscle cells with calcification medium. ERR\u03b3 expression in vascular smooth muscle cells was induced during calcification medium\u2013induced vascular calcification. Adenovirus-mediated overexpression of ERR\u03b3 in vascular smooth muscle cells resulted in the upregulation of the expression of osteogenic genes, including runt-related transcription factor 2, osteopontin, and Msx2, and the downregulation of \u03b1-smooth muscle actin. Adenovirus-mediated overexpression of ERR\u03b3 induced bone morphogenetic protein 2 (BMP2) expression, leading to increased phosphorylation of the intracellular BMP2 effector proteins SMAD1\/5\/8. Collectively, these data suggested that ERR\u03b3 promotes dedifferentiation of vascular smooth muscle cells to an osteogenic phenotype during the vascular calcification process. Inhibition of endogenous ERR\u03b3 expression or activity using a specific siRNA or the selective inverse agonist GSK5182 attenuated vascular calcification and osteogenic gene expression in vitro and in vivo.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The present results indicate that ERR\u03b3 plays a key role in vascular calcification by upregulating the BMP2 signaling pathway, suggesting that inhibition of ERR\u03b3 is a potential therapeutic strategy for the prevention of vascular calcification.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.306102","type":"journal-article","created":{"date-parts":[[2015,9,25]],"date-time":"2015-09-25T04:08:44Z","timestamp":1443154124000},"page":"2384-2390","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Estrogen-Related Receptor \u03b3 Plays a Key Role in Vascular Calcification Through the Upregulation of BMP2 Expression"],"prefix":"10.1161","volume":"35","author":[{"given":"Ji-Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease (Y.-K.C., J.-Y.D., Y.-K.C., J.-H.J., K.-G.P., I.-K.L.), Department of Biomedical..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon-Kyung","family":"Choi","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease (Y.-K.C., J.-Y.D., Y.-K.C., J.-H.J., K.-G.P., I.-K.L.), Department of Biomedical..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yeon","family":"Do","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease (Y.-K.C., J.-Y.D., Y.-K.C., J.-H.J., K.-G.P., I.-K.L.), Department of Biomedical..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Keun","family":"Choi","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease (Y.-K.C., J.-Y.D., Y.-K.C., J.-H.J., K.-G.P., I.-K.L.), Department of Biomedical..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chae-Myeong","family":"Ha","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; 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Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease (Y.-K.C., J.-Y.D., Y.-K.C., J.-H.J., K.-G.P., I.-K.L.), Department of Biomedical..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Kee","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease (Y.-K.C., J.-Y.D., Y.-K.C., J.-H.J., K.-G.P., I.-K.L.), Department of Biomedical..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hueng-Sik","family":"Choi","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine (J.-H.K., Y.-K.C., Y.-K.C., S.J.L., J.-H.J., K.-G.P., I.-K.L.), Research Institute of Aging and Metabolism (J.-H.K., S.J.L., K.-G.P., I.-K.L.), and BK21 Plus KNU Biomedical Convergence Program (C.-M.H., I.-K.L.), Kyungpook National University School of Medicine, Daegu, South Korea; 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