{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:05:53Z","timestamp":1771232753752,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,5,30]],"date-time":"2006-05-30T00:00:00Z","timestamp":1148947200000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Vascular calcification increasingly afflicts our aging and dysmetabolic population, predisposing patients to cardiovascular mortality and lower extremity amputation. Active osteogenic processes are evident in most histoanatomic variants, including elaboration of BMP2\u2010Msx2 signals required for craniofacial bone formation. We developed an animal model of diet\u2010induced diabetes, dyslipidemia, and vascular calcification. High\u2010fat diets promote vascular calcification in male low\u2010density lipoprotein receptor (LDLR)\u2010deficient mice, with concomitant upregulation of aortic BMP2 and Msx2 gene expression. We wished to test if Msx2 exerts pro\u2010calcific actions during vascular calcification, as it does in craniofacial bone. We studied CMV\u2010Msx2Tg+;LDLR+ transgenic mice (C57Bl\/6), a model previously demonstrated to recapitulate features of Msx2 signaling during craniosynostosis. After 16 weeks of fatty diets, vascular calcification was studied in CMV\u2010Msx2Tg+ versus nontransgenic sibs. Only CMV\u2010Msx2Tg+ mice fed high\u2010fat diets exhibited vascular calcium accumulation by alizarin red staining, noted in the tunica media of coronary arteries and the aorta. Gene expression studies revealed that while Msx2 was expressed primarily in adventitial cells, alkaline phosphatase (ALP) expression and calcification occurred primarily in the tunica media. Msx2 promotes the elaboration of a pro\u2010osteogenic milieu by upregulating expression of Wingless type (Wnt) ligands while downregulating the canonical antagonist, Dickkopf (Dkk1). Msx2 upregulates aortic Wnt signaling <jats:italic>in vivo<\/jats:italic>, revealed by the analysis of TOPGAL+ (Wnt reporter) versus CMV\u2010Msx2Tg+; TOPGAL+ mice. Aortic Msx2 exerts pro\u2010osteogenic signaling <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, mediated in part via the enhancement of paracrine Wnt signaling. Strategies that selectively inhibit aortic Msx2\u2010Wnt cascades may help diminish the initiation and progression of diabetic vascular disease.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1346.036","type":"journal-article","created":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T18:13:44Z","timestamp":1152555224000},"page":"327-333","source":"Crossref","is-referenced-by-count":74,"title":["Osteogenic Regulation of Vascular Calcification"],"prefix":"10.1111","volume":"1068","author":[{"given":"DWIGHT A.","family":"TOWLER","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JIAN\u2010SU","family":"SHAO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SU\u2010LI","family":"CHENG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JOYCE M.","family":"PINGSTERHAUS","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ARLEEN P.","family":"LOEWY","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,5,30]]},"reference":[{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00552.2003"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.1989.tb02747.x"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-172-41542"},{"key":"e_1_2_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000172633.74942.e6"},{"key":"e_1_2_3_6_2","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1172\/JCI116391","article-title":"Bone morphogenetic protein expression in human atherosclerotic lesions","volume":"91","author":"Bostrom K.","journal-title":"J. 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