{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:44:04Z","timestamp":1793227444406,"version":"4.5.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82060205"],"award-info":[{"award-number":["82060205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zunyi Science and Technology Plan Project","award":["Zun Shi Ke He HZ Zi [2023] 82"],"award-info":[{"award-number":["Zun Shi Ke He HZ Zi [2023] 82"]}]},{"name":"Zunyi Science and Technology Plan Project","award":["Zun Shi Ke He HZ Zi (2022) 423"],"award-info":[{"award-number":["Zun Shi Ke He HZ Zi (2022) 423"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-70688-w","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:03:53Z","timestamp":1724814233000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Metformin enhances the therapeutic effects of extracellular vesicles derived from human periodontal ligament stem cells on periodontitis"],"prefix":"10.1038","volume":"14","author":[{"given":"Mingli","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushuang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"70688_CR1","doi-asserted-by":"publisher","first-page":"2197779","DOI":"10.1080\/20002297.2023.2197779","volume":"15","author":"AA Abdulkareem","year":"2023","unstructured":"Abdulkareem, A. A. et al. Current concepts in the pathogenesis of periodontitis: From symbiosis to dysbiosis. J. Oral. Microbiol. 15, 2197779. https:\/\/doi.org\/10.1080\/20002297.2023.2197779 (2023).","journal-title":"J. Oral. Microbiol."},{"key":"70688_CR2","doi-asserted-by":"publisher","first-page":"766944","DOI":"10.3389\/fcimb.2021.766944","volume":"11","author":"LM Sedghi","year":"2021","unstructured":"Sedghi, L. M., Bacino, M. & Kapila, Y. L. Periodontal disease: The good, the bad, and the unknown. Front. Cell Infect. Microbiol. 11, 766944. https:\/\/doi.org\/10.3389\/fcimb.2021.766944 (2021).","journal-title":"Front. Cell Infect. Microbiol."},{"issue":"75","key":"70688_CR3","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/prd.12201","volume":"2000","author":"F Graziani","year":"2017","unstructured":"Graziani, F., Karapetsa, D., Alonso, B. & Herrera, D. Nonsurgical and surgical treatment of periodontitis: How many options for one disease?. Periodontol 2000(75), 152\u2013188. https:\/\/doi.org\/10.1111\/prd.12201 (2017).","journal-title":"Periodontol"},{"issue":"71","key":"70688_CR4","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/prd.12114","volume":"2000","author":"DE Deas","year":"2016","unstructured":"Deas, D. E., Moritz, A. J., Sagun, R. S. Jr., Gruwell, S. F. & Powell, C. A. Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis. Periodontol 2000(71), 128\u2013139. https:\/\/doi.org\/10.1111\/prd.12114 (2016).","journal-title":"Periodontol"},{"key":"70688_CR5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.reth.2019.12.011","volume":"14","author":"T Ouchi","year":"2020","unstructured":"Ouchi, T. & Nakagawa, T. Mesenchymal stem cell-based tissue regeneration therapies for periodontitis. Regen. Ther. 14, 72\u201378. https:\/\/doi.org\/10.1016\/j.reth.2019.12.011 (2020).","journal-title":"Regen. Ther."},{"key":"70688_CR6","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1111\/jre.12455","volume":"52","author":"SA Tassi","year":"2017","unstructured":"Tassi, S. A., Sergio, N. Z., Misawa, M. Y. O. & Villar, C. C. Efficacy of stem cells on periodontal regeneration: Systematic review of pre-clinical studies. J. Periodontal Res. 52, 793\u2013812. https:\/\/doi.org\/10.1111\/jre.12455 (2017).","journal-title":"J. Periodontal Res."},{"key":"70688_CR7","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1089\/scd.2019.0025","volume":"28","author":"O Trubiani","year":"2019","unstructured":"Trubiani, O. et al. Periodontal ligament stem cells: Current knowledge and future perspectives. Stem Cells Dev. 28, 995\u20131003. https:\/\/doi.org\/10.1089\/scd.2019.0025 (2019).","journal-title":"Stem Cells Dev."},{"key":"70688_CR8","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1080\/14712598.2023.2211203","volume":"23","author":"M Adelipour","year":"2023","unstructured":"Adelipour, M., Lubman, D. M. & Kim, J. Potential applications of mesenchymal stem cells and their derived exosomes in regenerative medicine. Expert Opin. Biol. Ther. 23, 491\u2013507. https:\/\/doi.org\/10.1080\/14712598.2023.2211203 (2023).","journal-title":"Expert Opin. Biol. Ther."},{"key":"70688_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512003","author":"GD Marconi","year":"2023","unstructured":"Marconi, G. D., Diomede, F., Pizzicannella, J. & Trubiani, O. Emerging role of oral mesenchymal stem\/stromal cells and their derivates. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms241512003 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"70688_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20204987","author":"O Trubiani","year":"2019","unstructured":"Trubiani, O. et al. Human oral stem cells, biomaterials and extracellular vesicles: A promising tool in bone tissue repair. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms20204987 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"70688_CR11","doi-asserted-by":"publisher","DOI":"10.1177\/00220345221084975","author":"C Yue","year":"2022","unstructured":"Yue, C. et al. Human bone marrow stromal cell exosomes ameliorate periodontitis. J. Dent. Res. https:\/\/doi.org\/10.1177\/00220345221084975 (2022).","journal-title":"J. Dent. Res."},{"key":"70688_CR12","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1089\/cell.2022.0147","volume":"25","author":"S Ma","year":"2023","unstructured":"Ma, S. et al. The emerging biological functions of exosomes from dental tissue-derived mesenchymal stem cells. Cell Reprogram 25, 53\u201364. https:\/\/doi.org\/10.1089\/cell.2022.0147 (2023).","journal-title":"Cell Reprogram"},{"key":"70688_CR13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12967-022-03487-4","volume":"20","author":"H Lin","year":"2022","unstructured":"Lin, H. et al. Advances of exosomes in periodontitis treatment. J. Transl. Med. 20, 279. https:\/\/doi.org\/10.1186\/s12967-022-03487-4 (2022).","journal-title":"J. Transl. Med."},{"key":"70688_CR14","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/j.gendis.2022.06.009","volume":"10","author":"T Zhang","year":"2023","unstructured":"Zhang, T. et al. Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis. Genes Dis. 10, 1613\u20131625. https:\/\/doi.org\/10.1016\/j.gendis.2022.06.009 (2023).","journal-title":"Genes Dis."},{"key":"70688_CR15","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1093\/stmcls\/sxac087","volume":"41","author":"Y Wang","year":"2023","unstructured":"Wang, Y. et al. Inflammatory periodontal ligament stem cells drive M1 macrophage polarization via exosomal miR-143\u20133p-mediated regulation of PI3K\/AKT\/NF-\u03baB signaling. Stem Cells 41, 184\u2013199. https:\/\/doi.org\/10.1093\/stmcls\/sxac087 (2023).","journal-title":"Stem Cells"},{"key":"70688_CR16","doi-asserted-by":"publisher","first-page":"113318","DOI":"10.1016\/j.yexcr.2022.113318","volume":"419","author":"C Lin","year":"2022","unstructured":"Lin, C. et al. Periodontal ligament fibroblasts-derived exosomes induced by PGE(2) inhibit human periodontal ligament stem cells osteogenic differentiation via activating miR-34c-5p\/SATB2\/ERK. Exp. Cell Res. 419, 113318. https:\/\/doi.org\/10.1016\/j.yexcr.2022.113318 (2022).","journal-title":"Exp. Cell Res."},{"key":"70688_CR17","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1016\/j.stemcr.2022.06.006","volume":"17","author":"HM Huang","year":"2022","unstructured":"Huang, H. M. et al. Mechanical force-promoted osteoclastic differentiation via periodontal ligament stem cell exosomal protein ANXA3. Stem Cell Rep. 17, 1842\u20131858. https:\/\/doi.org\/10.1016\/j.stemcr.2022.06.006 (2022).","journal-title":"Stem Cell Rep."},{"key":"70688_CR18","doi-asserted-by":"publisher","first-page":"1327405","DOI":"10.1155\/2020\/1327405","volume":"2020","author":"LL Zhou","year":"2020","unstructured":"Zhou, L. L. et al. Oral mesenchymal stem\/progenitor cells: The immunomodulatory masters. Stem Cells Int. 2020, 1327405. https:\/\/doi.org\/10.1155\/2020\/1327405 (2020).","journal-title":"Stem Cells Int."},{"key":"70688_CR19","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/jlb.4mr0421-750r","volume":"110","author":"Z Zhang","year":"2021","unstructured":"Zhang, Z., Deng, M., Hao, M. & Tang, J. Periodontal ligament stem cells in the periodontitis niche: Inseparable interactions and mechanisms. J. Leukoc. Biol. 110, 565\u2013576. https:\/\/doi.org\/10.1002\/jlb.4mr0421-750r (2021).","journal-title":"J. Leukoc. Biol."},{"key":"70688_CR20","doi-asserted-by":"publisher","first-page":"663037","DOI":"10.3389\/fcell.2021.663037","volume":"9","author":"Q Chen","year":"2021","unstructured":"Chen, Q. et al. Periodontal inflammation-triggered by periodontal ligament stem cell pyroptosis exacerbates periodontitis. Front. Cell Dev. Biol. 9, 663037. https:\/\/doi.org\/10.3389\/fcell.2021.663037 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"70688_CR21","doi-asserted-by":"publisher","first-page":"6679708","DOI":"10.1155\/2021\/6679708","volume":"2021","author":"GD Marconi","year":"2021","unstructured":"Marconi, G. D. et al. Ascorbic acid: A new player of epigenetic regulation in LPS-gingivalis treated human periodontal ligament stem cells. Oxid. Med. Cell Longev. 2021, 6679708. https:\/\/doi.org\/10.1155\/2021\/6679708 (2021).","journal-title":"Oxid. Med. Cell Longev."},{"key":"70688_CR22","doi-asserted-by":"publisher","first-page":"111423","DOI":"10.1016\/j.intimp.2023.111423","volume":"127","author":"W Wu","year":"2024","unstructured":"Wu, W. et al. Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis. Int. Immunopharmacol. 127, 111423. https:\/\/doi.org\/10.1016\/j.intimp.2023.111423 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"70688_CR23","doi-asserted-by":"publisher","first-page":"117324","DOI":"10.1016\/j.jep.2023.117324","volume":"319","author":"M Tang","year":"2024","unstructured":"Tang, M. et al. Flavonoid extract from propolis alleviates periodontitis by boosting periodontium regeneration and inflammation resolution via regulating TLR4\/MyD88\/NF-\u03baB and RANK\/NF-\u03baB pathway. J. Ethnopharmacol. 319, 117324. https:\/\/doi.org\/10.1016\/j.jep.2023.117324 (2024).","journal-title":"J. Ethnopharmacol."},{"key":"70688_CR24","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1111\/odi.14491","volume":"29","author":"J Cao","year":"2023","unstructured":"Cao, J. et al. Epigenetic regulation of osteogenic differentiation of periodontal ligament stem cells in periodontitis. Oral Dis. 29, 2529\u20132537. https:\/\/doi.org\/10.1111\/odi.14491 (2023).","journal-title":"Oral Dis."},{"key":"70688_CR25","doi-asserted-by":"publisher","first-page":"111717","DOI":"10.1016\/j.yexcr.2019.111717","volume":"386","author":"L Jia","year":"2020","unstructured":"Jia, L., Xiong, Y., Zhang, W., Ma, X. & Xu, X. Metformin promotes osteogenic differentiation and protects against oxidative stress-induced damage in periodontal ligament stem cells via activation of the Akt\/Nrf2 signaling pathway. Exp. Cell Res. 386, 111717. https:\/\/doi.org\/10.1016\/j.yexcr.2019.111717 (2020).","journal-title":"Exp. Cell Res."},{"key":"70688_CR26","doi-asserted-by":"publisher","first-page":"115743","DOI":"10.1016\/j.bcp.2023.115743","volume":"215","author":"ST Torunoglu","year":"2023","unstructured":"Torunoglu, S. T., Zajda, A., Tampio, J., Markowicz-Piasecka, M. & Huttunen, K. M. Metformin derivatives-Researchers\u2019 friends or foes?. Biochem. Pharmacol. 215, 115743. https:\/\/doi.org\/10.1016\/j.bcp.2023.115743 (2023).","journal-title":"Biochem. Pharmacol."},{"key":"70688_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010755","author":"I Nojima","year":"2023","unstructured":"Nojima, I. & Wada, J. Metformin and its immune-mediated effects in various diseases. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms24010755 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"70688_CR28","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1515\/jbcpp-2022-0252","volume":"34","author":"A Naseri","year":"2023","unstructured":"Naseri, A. et al. Metformin: New applications for an old drug. J. Basic Clin. Physiol. Pharmacol. 34, 151\u2013160. https:\/\/doi.org\/10.1515\/jbcpp-2022-0252 (2023).","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"70688_CR29","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41574-023-00833-4","volume":"19","author":"M Foretz","year":"2023","unstructured":"Foretz, M., Guigas, B. & Viollet, B. Metformin: update on mechanisms of action and repurposing potential. Nat. Rev. Endocrinol. 19, 460\u2013476. https:\/\/doi.org\/10.1038\/s41574-023-00833-4 (2023).","journal-title":"Nat. Rev. Endocrinol."},{"key":"70688_CR30","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.jtumed.2023.03.014","volume":"18","author":"UMK Hammad","year":"2023","unstructured":"Hammad, U. M. K. et al. Applications of metformin in dentistry-a review. J. Taibah Univ. Med. Sci. 18, 1299\u20131310. https:\/\/doi.org\/10.1016\/j.jtumed.2023.03.014 (2023).","journal-title":"J. Taibah Univ. Med. Sci."},{"key":"70688_CR31","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/cbin.11202","volume":"44","author":"R Zhang","year":"2020","unstructured":"Zhang, R., Liang, Q., Kang, W. & Ge, S. Metformin facilitates the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells in vitro. Cell Biol. Int. 44, 70\u201379. https:\/\/doi.org\/10.1002\/cbin.11202 (2020).","journal-title":"Cell Biol. Int."},{"key":"70688_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.dental.2023.07.008","author":"Y Sun","year":"2023","unstructured":"Sun, Y. et al. Injectable periodontal ligament stem cell-metformin-calcium phosphate scaffold for bone regeneration and vascularization in rats. Dent Mater. https:\/\/doi.org\/10.1016\/j.dental.2023.07.008 (2023).","journal-title":"Dent Mater."},{"key":"70688_CR33","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.joen.2023.07.005","volume":"49","author":"CY Hong","year":"2023","unstructured":"Hong, C. Y. et al. Metformin reduces bone resorption in apical periodontitis through regulation of osteoblast and osteoclast differentiation. J. Endod. 49, 1129\u20131137. https:\/\/doi.org\/10.1016\/j.joen.2023.07.005 (2023).","journal-title":"J. Endod."},{"key":"70688_CR34","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1016\/j.joen.2018.08.002","volume":"44","author":"EH Lai","year":"2018","unstructured":"Lai, E. H. et al. Metformin ameliorates periapical lesions through suppression of hypoxia-induced apoptosis of osteoblasts. J. Endod. 44, 1817\u20131825. https:\/\/doi.org\/10.1016\/j.joen.2018.08.002 (2018).","journal-title":"J. Endod."},{"key":"70688_CR35","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.arcmed.2020.10.007","volume":"52","author":"H Soraya","year":"2021","unstructured":"Soraya, H., Sani, N. A., Jabbari, N. & Rezaie, J. Metformin increases exosome biogenesis and secretion in U87\u00a0MG human glioblastoma cells: A possible mechanism of therapeutic resistance. Arch. Med. Res. 52, 151\u2013162. https:\/\/doi.org\/10.1016\/j.arcmed.2020.10.007 (2021).","journal-title":"Arch. Med. Res."},{"key":"70688_CR36","doi-asserted-by":"publisher","first-page":"120850","DOI":"10.1016\/j.biomaterials.2021.120850","volume":"274","author":"Z Liao","year":"2021","unstructured":"Liao, Z. et al. Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration. Biomaterials 274, 120850. https:\/\/doi.org\/10.1016\/j.biomaterials.2021.120850 (2021).","journal-title":"Biomaterials"},{"key":"70688_CR37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s10522-019-09838-x","volume":"21","author":"Y Kuang","year":"2020","unstructured":"Kuang, Y. et al. Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells. Biogerontology 21, 13\u201327. https:\/\/doi.org\/10.1007\/s10522-019-09838-x (2020).","journal-title":"Biogerontology"},{"key":"70688_CR38","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1111\/jre.12912","volume":"56","author":"B Zhang","year":"2021","unstructured":"Zhang, B., Yang, Y., Yi, J., Zhao, Z. & Ye, R. Hyperglycemia modulates M1\/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis. J. Periodontal Res. 56, 991\u20131005. https:\/\/doi.org\/10.1111\/jre.12912 (2021).","journal-title":"J. Periodontal Res."},{"key":"70688_CR39","doi-asserted-by":"publisher","first-page":"115263","DOI":"10.1016\/j.biopha.2023.115263","volume":"165","author":"A Malaekeh-Nikouei","year":"2023","unstructured":"Malaekeh-Nikouei, A. et al. Metformin beyond an anti-diabetic agent: A comprehensive and mechanistic review on its effects against natural and chemical toxins. Biomed. Pharmacother. 165, 115263. https:\/\/doi.org\/10.1016\/j.biopha.2023.115263 (2023).","journal-title":"Biomed. Pharmacother."},{"key":"70688_CR40","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1007\/s11684-023-0998-6","volume":"17","author":"Y Dong","year":"2023","unstructured":"Dong, Y. et al. The development and benefits of metformin in various diseases. Front. Med. 17, 388\u2013431. https:\/\/doi.org\/10.1007\/s11684-023-0998-6 (2023).","journal-title":"Front. Med."},{"key":"70688_CR41","doi-asserted-by":"publisher","first-page":"1036885","DOI":"10.3389\/fendo.2022.1036885","volume":"13","author":"CH Tseng","year":"2022","unstructured":"Tseng, C. H. Metformin and risk of gingival\/periodontal diseases in diabetes patients: A retrospective cohort study. Front. Endocrinol. (Lausanne) 13, 1036885. https:\/\/doi.org\/10.3389\/fendo.2022.1036885 (2022).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"70688_CR42","doi-asserted-by":"publisher","first-page":"18","DOI":"10.4103\/ccd.ccd_271_20","volume":"13","author":"KS Patil","year":"2022","unstructured":"Patil, K. S. et al. Efficacy of 1.5% metformin gel as an adjuvant to scaling, root planing, and curettage for the treatment of infrabony defects in chronic periodontitis patients. Contemp. Clin. Dent. 13, 18\u201323. https:\/\/doi.org\/10.4103\/ccd.ccd_271_20 (2022).","journal-title":"Contemp. Clin. Dent."},{"key":"70688_CR43","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00828-0","author":"TJ de Vries","year":"2023","unstructured":"de Vries, T. J., Kleemann, A. S., Jin, J. & Schoenmaker, T. The differential effect of metformin on osteocytes, osteoblasts, and osteoclasts. Curr. Osteoporos. Rep. https:\/\/doi.org\/10.1007\/s11914-023-00828-0 (2023).","journal-title":"Curr. Osteoporos. Rep."},{"key":"70688_CR44","doi-asserted-by":"publisher","first-page":"687258","DOI":"10.3389\/fcell.2021.687258","volume":"9","author":"D Fei","year":"2021","unstructured":"Fei, D. et al. Exosomes regulate interclonal communication on osteogenic differentiation among heterogeneous osteogenic single-cell clones through PINK1\/Parkin-mediated mitophagy. Front. Cell Dev. Biol. 9, 687258. https:\/\/doi.org\/10.3389\/fcell.2021.687258 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"70688_CR45","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.3389\/fimmu.2019.01310","volume":"10","author":"Z Wang","year":"2019","unstructured":"Wang, Z. et al. Cyclic stretch force induces periodontal ligament cells to secrete exosomes that suppress IL-1\u03b2 production through the inhibition of the NF-\u03baB signaling pathway in macrophages. Front. Immunol. 10, 1310. https:\/\/doi.org\/10.3389\/fimmu.2019.01310 (2019).","journal-title":"Front. Immunol."},{"key":"70688_CR46","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1089\/scd.2019.0031","volume":"28","author":"A Tomokiyo","year":"2019","unstructured":"Tomokiyo, A., Wada, N. & Maeda, H. Periodontal ligament stem cells: Regenerative potency in periodontium. Stem Cells Dev. 28, 974\u2013985. https:\/\/doi.org\/10.1089\/scd.2019.0031 (2019).","journal-title":"Stem Cells Dev."},{"key":"70688_CR47","doi-asserted-by":"publisher","first-page":"519","DOI":"10.2147\/ijn.S346755","volume":"17","author":"B Zhao","year":"2022","unstructured":"Zhao, B. et al. Periodontal ligament stem cell-derived small extracellular vesicles embedded in matrigel enhance bone repair through the adenosine receptor signaling pathway. Int. J. Nanomed. 17, 519\u2013536. https:\/\/doi.org\/10.2147\/ijn.S346755 (2022).","journal-title":"Int. J. Nanomed."},{"key":"70688_CR48","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14102189","author":"Y Zhao","year":"2022","unstructured":"Zhao, Y. et al. The experimental study of periodontal ligament stem cells derived exosomes with hydrogel accelerating bone regeneration on alveolar bone defect. Pharmaceutics https:\/\/doi.org\/10.3390\/pharmaceutics14102189 (2022).","journal-title":"Pharmaceutics"},{"key":"70688_CR49","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.actbio.2021.12.035","volume":"141","author":"F Lei","year":"2022","unstructured":"Lei, F. et al. Treatment of inflammatory bone loss in periodontitis by stem cell-derived exosomes. Acta Biomater. 141, 333\u2013343. https:\/\/doi.org\/10.1016\/j.actbio.2021.12.035 (2022).","journal-title":"Acta Biomater."},{"key":"70688_CR50","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1002\/sctm.19-0418","volume":"9","author":"XY Xu","year":"2020","unstructured":"Xu, X. Y. et al. Exosomes derived from P2X7 receptor gene-modified cells rescue inflammation-compromised periodontal ligament stem cells from dysfunction. Stem Cells Transl. Med. 9, 1414\u20131430. https:\/\/doi.org\/10.1002\/sctm.19-0418 (2020).","journal-title":"Stem Cells Transl. Med."},{"key":"70688_CR51","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1089\/scd.2019.0021","volume":"28","author":"A \u010cebatari\u016bnien\u0117","year":"2019","unstructured":"\u010cebatari\u016bnien\u0117, A., Kriau\u010di\u016bnait\u0117, K., Prunskait\u0117, J., Tunaitis, V. & Pivori\u016bnas, A. Extracellular vesicles suppress basal and lipopolysaccharide-induced NF\u03baB activity in human periodontal ligament stem cells. Stem Cells Dev. 28, 1037\u20131049. https:\/\/doi.org\/10.1089\/scd.2019.0021 (2019).","journal-title":"Stem Cells Dev."},{"key":"70688_CR52","doi-asserted-by":"publisher","DOI":"10.1159\/000519569","author":"XD Han","year":"2021","unstructured":"Han, X. D., Chen, H. M. & Li, C. Effect of human periodontal ligament stem cell-derived extracellular vesicles on macrophage pyroptosis and periodontal inflammatory injury in periodontitis. Cells Tissues Organs https:\/\/doi.org\/10.1159\/000519569 (2021).","journal-title":"Cells Tissues Organs"},{"key":"70688_CR53","doi-asserted-by":"publisher","first-page":"3843","DOI":"10.3390\/ijms19123843","volume":"19","author":"H Kang","year":"2018","unstructured":"Kang, H., Lee, M. J., Park, S. J. & Lee, M. S. Lipopolysaccharide-preconditioned periodontal ligament stem cells induce M1 polarization of macrophages through extracellular vesicles. Int. J. Mol. Sci. 19, 3843. https:\/\/doi.org\/10.3390\/ijms19123843 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"70688_CR54","doi-asserted-by":"publisher","first-page":"20662","DOI":"10.1002\/jcp.28671","volume":"234","author":"Y Zheng","year":"2019","unstructured":"Zheng, Y. et al. Exosomal microRNA-155\u20135p from PDLSCs regulated Th17\/Treg balance by targeting sirtuin-1 in chronic periodontitis. J. Cell Physiol. 234, 20662\u201320674. https:\/\/doi.org\/10.1002\/jcp.28671 (2019).","journal-title":"J. Cell Physiol."},{"key":"70688_CR55","doi-asserted-by":"publisher","first-page":"558","DOI":"10.7150\/ijms.40918","volume":"17","author":"Z Zhang","year":"2020","unstructured":"Zhang, Z. et al. PDLSCs regulate angiogenesis of periodontal ligaments via VEGF transferred by exosomes in periodontitis. Int. J. Med. Sci. 17, 558\u2013567. https:\/\/doi.org\/10.7150\/ijms.40918 (2020).","journal-title":"Int. J. Med. Sci."},{"key":"70688_CR56","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.addr.2018.12.009","volume":"138","author":"M Piffoux","year":"2019","unstructured":"Piffoux, M. et al. Extracellular vesicles for personalized medicine: The input of physically triggered production, loading and theranostic properties. Adv. Drug Deliv. Rev. 138, 247\u2013258. https:\/\/doi.org\/10.1016\/j.addr.2018.12.009 (2019).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"70688_CR57","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s11658-023-00422-3","volume":"28","author":"X Li","year":"2023","unstructured":"Li, X. et al. Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles. Cell Mol. Biol. Lett. 28, 9. https:\/\/doi.org\/10.1186\/s11658-023-00422-3 (2023).","journal-title":"Cell Mol. Biol. Lett."},{"key":"70688_CR58","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.actbio.2022.07.015","volume":"150","author":"Y Zhuang","year":"2022","unstructured":"Zhuang, Y. et al. Small extracellular vesicles derived from hypoxic mesenchymal stem cells promote vascularized bone regeneration through the miR-210\u20133p\/EFNA3\/PI3K pathway. Acta Biomater. 150, 413\u2013426. https:\/\/doi.org\/10.1016\/j.actbio.2022.07.015 (2022).","journal-title":"Acta Biomater."},{"key":"70688_CR59","doi-asserted-by":"publisher","first-page":"112646","DOI":"10.1016\/j.msec.2022.112646","volume":"133","author":"W Yu","year":"2022","unstructured":"Yu, W. et al. Higher yield and enhanced therapeutic effects of exosomes derived from MSCs in hydrogel-assisted 3D culture system for bone regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 133, 112646. https:\/\/doi.org\/10.1016\/j.msec.2022.112646 (2022).","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"70688_CR60","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.pbiomolbio.2006.07.021","volume":"93","author":"L Claes","year":"2007","unstructured":"Claes, L. & Willie, B. The enhancement of bone regeneration by ultrasound. Prog. Biophys. Mol. Biol. 93, 384\u2013398. https:\/\/doi.org\/10.1016\/j.pbiomolbio.2006.07.021 (2007).","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"70688_CR61","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s13346-013-0171-x","volume":"4","author":"H Hau","year":"2014","unstructured":"Hau, H., Rohanizadeh, R., Ghadiri, M. & Chrzanowski, W. A mini-review on novel intraperiodontal pocket drug delivery materials for the treatment of periodontal diseases. Drug Deliv. Transl. Res. 4, 295\u2013301. https:\/\/doi.org\/10.1007\/s13346-013-0171-x (2014).","journal-title":"Drug Deliv. Transl. Res."},{"key":"70688_CR62","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217885","author":"P Simeone","year":"2020","unstructured":"Simeone, P. et al. Diameters and fluorescence calibration for extracellular vesicle analyses by flow cytometry. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms21217885 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"70688_CR63","doi-asserted-by":"publisher","first-page":"e12404","DOI":"10.1002\/jev2.12404","volume":"13","author":"JA Welsh","year":"2024","unstructured":"Welsh, J. A. et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J. Extracell Ves. 13, e12404. https:\/\/doi.org\/10.1002\/jev2.12404 (2024).","journal-title":"J. Extracell Ves."},{"key":"70688_CR64","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1016\/j.cmet.2023.10.013","volume":"35","author":"S Ma","year":"2023","unstructured":"Ma, S. et al. Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk. Cell Metab 35, 2028\u201320432027. https:\/\/doi.org\/10.1016\/j.cmet.2023.10.013 (2023).","journal-title":"Cell Metab"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70688-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70688-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70688-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:14:53Z","timestamp":1724814893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70688-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,27]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["70688"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-70688-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,27]]},"assertion":[{"value":"12 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19940"}}