{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:09:41Z","timestamp":1782742181042,"version":"3.54.5"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["In Vitro Cell.Dev.Biol.-Animal"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Valvular interstitial cells (VICs) are integral to the progression of calcific aortic valve disease (CAVD). Dentin matrix protein-1 (DMP-1), a member of the Sibling family protein, is implicated in the calcification process. This study aims to investigate the role and mechanisms of DMP-1 in the osteogenic differentiation of VICs. Between April 2018 and December 2018, aortic valve tissues were collected from 14 patients undergoing aortic valve replacement or heart transplantation. DMP-1 expression was quantified in calcified valves versus normal controls. An in vitro model of VICs\u2019 osteogenic differentiation was established to study the regulatory mechanism of DMP-1 on valvular calcification using immunoblot, immunohistochemistry, immunofluorescence, etc. The expression of DMP-1 was significantly increased in the calcified aortic valves patients (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). DMP-1, both short and long arginine-glycine-aspartic acid (RGD) peptides, induced the osteogenic differentiation in VICs, an effect that was inhibited by an integrin \u03b1v\u03b23 antagonist (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Furthermore, the expression levels of RAF, RAS, MEK, and phosphorylated ERK1\/2 were significantly elevated in VICs upon stimulation of DMP-1 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). DMP-1 is involved in the progression of valvular calcification and promotes the osteogenic differentiation of VICs via the integrin \u03b1v\u03b23 receptor. The combination of DMP-1 and integrin \u03b1v\u03b23 via its RGD domain activates the MAPK signaling pathway, leading to enhanced osteogenic gene expression in VICs. Clinical trial number: not applicable.\n                  <\/jats:p>","DOI":"10.1007\/s11626-025-01101-7","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:57:47Z","timestamp":1760367467000},"page":"1057-1070","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dentin matrix protein-1 promoted osteogenic differentiation of valvular interstitial cells via MAPK signal pathway during aortic valve calcification"],"prefix":"10.1007","volume":"61","author":[{"given":"Jinjie","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"1101_CR1","doi-asserted-by":"publisher","first-page":"6593","DOI":"10.1016\/j.biomaterials.2009.08.031","volume":"30","author":"JA Benton","year":"2009","unstructured":"Benton JA, Fairbanks BD, Anseth KS (2009) Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels. 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