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To elucidate the role that periostin plays in the developing heart we analyzed cardiac OFT phenotype in mice after deletion of the Postn gene. We found that lack of periostin in the embryonic OFT leads to ectopic expression of the proosteogenic growth factor pleiotrophin ( Ptn) and overexpression of delta-like 1 homolog (Dlk1), a negative regulator of Notch1, in the distal (prevalvular) cushions of the OFT. This resulted in suppression of Notch1 signaling, strong induction of the central transcriptional regulator of osteoblast cell fate Runx2, upregulation of osteopontin and osteocalcin expression, and subsequent calcification of the aortic valve. Our data suggest that periostin represses a default osteogenic program in the OFT cushion mesenchyme and promotes differentiation along a fibrogenic lineage. Lack of periostin causes derepression of the osteogenic potential of OFT mesenchymal cells, calcium deposition, and calcific aortic valve disease. These results establish periostin as a key regulator of OFT endocardial cushion mesenchymal cell fate during embryonic development.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00078.2009","type":"journal-article","created":{"date-parts":[[2009,9,2]],"date-time":"2009-09-02T02:24:14Z","timestamp":1251858254000},"page":"160-168","source":"Crossref","is-referenced-by-count":79,"title":["Lack of periostin leads to suppression of Notch1 signaling and calcific aortic valve disease"],"prefix":"10.1152","volume":"39","author":[{"given":"Tatiana V.","family":"Tkatchenko","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo A.","family":"Moreno-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger R.","family":"Markwald","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei V.","family":"Tkatchenko","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.654913"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.10.001"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00081-9"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000256957.10242.75"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2005.06.002"},{"key":"B6","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1242\/dev.126.12.2631","volume":"126","author":"Clark TG","year":"1999","journal-title":"Development"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.03.050"},{"key":"B8","doi-asserted-by":"crossref","unstructured":"de la Cruz MV , Markwald RR .Living Morphogenesis of the Heart. 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