{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:45:31Z","timestamp":1790610331517,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,4,21]],"date-time":"2010-04-21T00:00:00Z","timestamp":1271808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vascular calcification is a major risk factor for cardiovascular morbidity and mortality. Smooth muscle cells (SMCs) may play an important role in vascular cartilaginous metaplasia and calcification via reprogramming to the osteochondrogenic state. To study whether SM lineage reprogramming and thus matrix calcification is reversible and what the necessary regulatory factors are to reverse this process, we used cells isolated from calcifying arterial medias of 4\u2010week\u2010old matrix Gla protein knockout mice (MGP\u2212\/\u2212SMCs). We found that vascular cells with an osteochondrogenic phenotype regained SMC properties (positive for SM22\u03b1 and SM \u03b1\u2010actin) and down\u2010regulated osteochondrogenic gene expression (Runx2\/Cbfa1 and osteopontin) upon culture in medium that favors SMC differentiation. Over time, the MGP\u2212\/\u2212 SMCs no longer expressed osteochondrogenic proteins and became indistinguishable from wild\u2010type SMCs. Moreover, phenotypic switch of the restored SMCs to the osteochondrogenic state was re\u2010induced by the pro\u2010calcific factor, inorganic phosphate. Finally, loss\u2010 and gain\u2010of\u2010function studies of myocardin, a SM\u2010specific transcription co\u2010activator, and Runx2\/Cbfa1, an osteochondrogenic transcription factor, revealed that upregulation of Runx2\/Cbfa1, but not loss of myocardin, played a critical role in phosphate\u2010induced SMC lineage reprogramming and calcification. These results are the first to demonstrate reversibility of vascular SMCs in the osteochondrogenic state in response to local environmental cues, and that myocardin\u2010enforced SMC lineage allocation was not sufficient to block vascular calcification. On the other hand, Runx2\/Cbfa1 was found to be a decisive factor identified in the process. J. Cell. Biochem. 110: 935\u2013947, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22607","type":"journal-article","created":{"date-parts":[[2010,4,21]],"date-time":"2010-04-21T14:05:34Z","timestamp":1271858734000},"page":"935-947","source":"Crossref","is-referenced-by-count":126,"title":["Runx2\/Cbfa1, but not loss of myocardin, is required for smooth muscle cell lineage reprogramming toward osteochondrogenesis"],"prefix":"10.1002","volume":"110","author":[{"given":"Mei Y.","family":"Speer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranoti G.","family":"Hiremath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia 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