{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:40:15Z","timestamp":1792662015369,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dental pulp stem cells (DPSCs) possess multilineage differentiation potential and contribute to dental pulp regeneration through odontoblast replacement and neovascularization. Although mechanosensitive ion channels such as PIEZO1 are known to regulate stem cell fate, their role in DPSC\u2010mediated angiogenesis under mechanical stress remains poorly understood. In this study, we investigated the involvement of PIEZO1 in regulating angiogenic gene expression and endothelial differentiation of immortalized human DPSCs (hDPSC\u2010K4DT). Compressive force was applied using an in vitro weight\u2010loading model previously developed to mimic the mechanical stress present in the pulp microenvironment. RT\u2010qPCR analysis revealed that\n                    <jats:italic>VEGFA<\/jats:italic>\n                    expression was significantly upregulated following pressure loading. Additionally, activation of PIEZO1 using Yoda1, a specific chemical agonist, further enhanced the expression of\n                    <jats:italic>VEGFA<\/jats:italic>\n                    ,\n                    <jats:italic>HIF\u20101\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>bFGF<\/jats:italic>\n                    , without affecting markers of hard tissue differentiation. Conversely, siRNA\u2010mediated knockdown of the mechanosensitive ion channel PIEZO1 attenuated the upregulation of angiogenesis\u2010related genes and inhibited the formation of capillary\u2010like structures in a 3D spheroid sprouting assay. These results indicate that PIEZO1 acts as a mechanosensor mediating angiogenic signaling in DPSCs, thereby promoting endothelial differentiation and capillary morphogenesis. Mechanical stimuli such as compressive force, occlusal loading, or orthodontic pressure may activate PIEZO1 in pulp\u2010resident stem cells and thereby promote vascular regeneration. In conclusion, PIEZO1 functions as a key mechanotransduction channel that regulates angiogenesis\u2010related gene expression and vascular structure formation in DPSCs. Modulating PIEZO1 activity could enhance the angiogenic capacity of DPSCs, offering a promising strategy for vascularized dental pulp regeneration in regenerative endodontics.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70327","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:01:01Z","timestamp":1792659661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanosensitive PIEZO1 Regulates Angiogenic Signaling in Human Dental Pulp Stem Cells"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7153-9367","authenticated-orcid":false,"given":"Ai","family":"Orimoto","sequence":"first","affiliation":[{"name":"Division of Endodontics and Restorative Dentistry Kyushu Dental University Kitakyushu Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-6624","authenticated-orcid":false,"given":"Chihiro","family":"Nakatomi","sequence":"additional","affiliation":[{"name":"Division of Physiology Kyushu Dental University Kitakyushu Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Division of Endodontics and Restorative Dentistry Kyushu Dental University Kitakyushu Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-7705","authenticated-orcid":false,"given":"Kentaro","family":"Ono","sequence":"additional","affiliation":[{"name":"Division of Physiology Kyushu Dental University Kitakyushu Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.joen.2006.09.013","article-title":"Regenerative Endodontics: A Review of Current Status and a Call for Action","volume":"33","author":"Murray P. 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R.Munoz \u201cAngiogenic Mechanisms of Human Dental Pulp and Their Relationship With Substance P Expression in Response to Occlusal Trauma \u201dInternational Endodontic Journal50 no. 4 (April2017): 339\u2013351 https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iej.12627.","DOI":"10.1111\/iej.12627"},{"issue":"9","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1177\/154405910608500908","article-title":"Role of Human Pulp Fibroblasts in Angiogenesis","volume":"85","author":"Tran\u2010Hung L.","year":"2006","journal-title":"Journal of Dental Research"},{"issue":"12","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1177\/00220345211007427","article-title":"Fabrication of Vascularized DPSC Constructs for Efficient Pulp Regeneration","volume":"100","author":"Katata C.","year":"2021","journal-title":"Journal of Dental Research"},{"issue":"3","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3390\/ijms20030526","article-title":"The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain","volume":"20","author":"Hossain M. 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Z.Zheng et al. \u201cKinetic Expression of Platelet Endothelial Cell Adhesion Molecule\u20101 (PECAM\u20101\/CD31) During Embryonic Stem Cell Differentiation \u201dJournal of Cellular Biochemistry95 (2005): 559\u2013570.","DOI":"10.1002\/jcb.20436"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70327","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbf.70327","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70327","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:01:06Z","timestamp":1792659666000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.70327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/cbf.70327"],"URL":"https:\/\/doi.org\/10.1002\/cbf.70327","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70327"}}