{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:21:20Z","timestamp":1791138080674,"version":"4.1.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,3,5]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Calcification of heart valve structures is the most common form of valvular disease and is characterized by the appearance of bone-like phenotypes within affected structures. Despite the clinical significance, the underlying etiology of disease onset and progression is largely unknown and valve replacement remains the most effective treatment. The SRY-related transcription factor\n            <jats:italic>Sox9<\/jats:italic>\n            is expressed in developing and mature heart valves, and its function is required for expression of cartilage-associated proteins, similar to its role in chondrogenesis. In addition to cartilage-associated defects, mice with reduced sox9 function develop skeletal bone prematurely; however, the ability of sox9 deficiency to promote ectopic osteogenic phenotypes in heart valves has not been examined.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            This study aims to determine the role of\n            <jats:italic>Sox9<\/jats:italic>\n            in maintaining connective tissue homeostasis in mature heart valves using in vivo and in vitro approaches.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Using histological and molecular analyses, we report that, from 3 months of age,\n            <jats:italic>Sox9<\/jats:italic>\n            <jats:sup>\n              <jats:italic>fl<\/jats:italic>\n              \/+\n            <\/jats:sup>\n            <jats:italic>;Col2a1-cre<\/jats:italic>\n            mice develop calcific lesions in heart valve leaflets associated with increased expression of bone-related genes and activation of inflammation and matrix remodeling processes. Consistently, ectopic calcification is also observed following direct knockdown of\n            <jats:italic>Sox9<\/jats:italic>\n            in heart valves in vitro. Furthermore, we show that retinoic acid treatment in mature heart valves is sufficient to promote calcific processes in vitro, which can be attenuated by\n            <jats:italic>Sox9<\/jats:italic>\n            overexpression.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            This study provides insight into the molecular mechanisms of heart valve calcification and identifies reduced\n            <jats:italic>Sox9<\/jats:italic>\n            function as a potential genetic basis for calcific valvular disease.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.213702","type":"journal-article","created":{"date-parts":[[2010,1,8]],"date-time":"2010-01-08T04:46:17Z","timestamp":1262925977000},"page":"712-719","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["Reduced Sox9 Function Promotes Heart Valve Calcification Phenotypes In Vivo"],"prefix":"10.1161","volume":"106","author":[{"given":"Jacqueline D.","family":"Peacock","sequence":"first","affiliation":[{"name":"From the Molecular and Cellular Pharmacology Graduate Program (J.D.P.); Department of Molecular and Cellular Pharmacology (A.K.L., G.T., J.L.); Leonard M. Miller School of Medicine (D.B.G.); Molecular Cell and Developmental Biology Graduate Program (G.T.); and Department of Medicine (J.L.), Leonard M. Miller School of Medicine, University of Miami, Fla."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata K.","family":"Levay","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Pharmacology Graduate Program (J.D.P.); Department of Molecular and Cellular Pharmacology (A.K.L., G.T., J.L.); Leonard M. Miller School of Medicine (D.B.G.); Molecular Cell and Developmental Biology Graduate Program (G.T.); and Department of Medicine (J.L.), Leonard M. Miller School of Medicine, University of Miami, Fla."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin B.","family":"Gillaspie","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Pharmacology Graduate Program (J.D.P.); Department of Molecular and Cellular Pharmacology (A.K.L., G.T., J.L.); Leonard M. Miller School of Medicine (D.B.G.); Molecular Cell and Developmental Biology Graduate Program (G.T.); and Department of Medicine (J.L.), Leonard M. Miller School of Medicine, University of Miami, Fla."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Tao","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Pharmacology Graduate Program (J.D.P.); Department of Molecular and Cellular Pharmacology (A.K.L., G.T., J.L.); Leonard M. Miller School of Medicine (D.B.G.); Molecular Cell and Developmental Biology Graduate Program (G.T.); and Department of Medicine (J.L.), Leonard M. Miller School of Medicine, University of Miami, Fla."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Lincoln","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Pharmacology Graduate Program (J.D.P.); Department of Molecular and Cellular Pharmacology (A.K.L., G.T., J.L.); Leonard M. 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