{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:25:23Z","timestamp":1791350723590,"version":"4.3.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970947"],"award-info":[{"award-number":["81970947"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771095"],"award-info":[{"award-number":["81771095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700971"],"award-info":[{"award-number":["81700971"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Previously, our investigations demonstrated robust pro\u2010angiogenic potentials of extracellular vesicles secreted by periodontitis\u2010compromised dental pulp stem cells (P\u2010EVs) when compared to those from healthy DPSCs (H\u2010EVs), but the underlying mechanism remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Here, circulating microRNAs (miRNAs) specifically found in P\u2010EVs (compared with H\u2010EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P\u2010EV\u2010enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK\u20108, transwell\/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog\/Gli1 signalling pathway components and angiogenesis\u2010related factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The angiogenesis\u2010related miRNA miR\u2010378a was found to be enriched in P\u2010EVs, and its role in P\u2010EV\u2010enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR\u2010378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog\/Gli1 signalling. Further, we found that incubation with P\u2010EVs enabled the transmission of P\u2010EV\u2010contained miR\u2010378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P\u2010EV\u2010mediated miR\u2010378a transmission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest that P\u2010EVs carrying miR\u2010378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog\/Gli1 signalling pathway. Our findings reveal a crucial role for EV\u2010derived miR\u2010378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.13026","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T02:31:00Z","timestamp":1616553060000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Periodontitis\u2010compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA\u2010378a promote local angiogenesis by targeting Sufu to activate the Hedgehog\/Gli1 signalling"],"prefix":"10.1111","volume":"54","author":[{"given":"Huan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"},{"name":"Shaanxi Key Laboratory of Free Radical Biology and Medicine The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Xin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Tao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"An","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Yue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"},{"name":"Shaanxi Key Laboratory of Free Radical Biology and Medicine The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Hua","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010An","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-2104","authenticated-orcid":false,"given":"Fa\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Stomatology State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture Fourth Military Medical University Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.08.003"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2618"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01614-w"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12144"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0551-0"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0309-228"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.608521"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1196-y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.03.002"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb0322s30"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07810-w"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808855115"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201904044"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.08.010"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.21234"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.22958"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.36388"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1371-1"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706901104"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8110483"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780252"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12002"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2575"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1609206"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1815447116"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071450"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.44"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-1069-9"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12027"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0297"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt520"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945010791591313"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.04.002"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5184"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000116"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00979-w"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2020.1826632"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0752-1"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02799-x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01989-w"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00421-16"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.421"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.116"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-008-9105-5"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/dj6040072"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0633-z"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01685"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/2041731420975569"}],"updated-by":[{"DOI":"10.1111\/cpr.13306","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000}}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.13026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T16:39:57Z","timestamp":1692463197000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.13026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,23]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/cpr.13026"],"URL":"https:\/\/doi.org\/10.1111\/cpr.13026","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,23]]},"assertion":[{"value":"2021-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13026"}}