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Human dental follicle stem cell-derived exosomes reduce root resorption by inhibiting periodontal ligament cell pyroptosis.

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Title: Human dental follicle stem cell-derived exosomes reduce root resorption by inhibiting periodontal ligament cell pyroptosis.
Authors: Li, Xinyi1 (AUTHOR), Liu, Xinyang1 (AUTHOR), Zhou, Jianing1 (AUTHOR), Zhang, Ping1 (AUTHOR), Chen, Song1 (AUTHOR) chensong@scu.edu.cn, Bai, Ding1 (AUTHOR) baiding@scu.edu.cn
Source: Stem Cell Research & Therapy. 2/21/2025, Vol. 16 Issue 1, p1-15. 15p.
Subject Terms: *SUPPRESSORS of cytokine signaling, *ROOT resorption (Teeth), *CYTOLOGY, *PERIODONTAL ligament, *LIFE sciences
Abstract: Background: To explore the therapeutic effects and mechanisms of the exosomes derived from dental follicle stem cells (DFSC-Exos) in reducing osteoclastogenesis and root resorption (RR) by inhibiting periodontal ligament cell (PDLC) pyroptosis. Methods: DFSC-Exos, with force stimulation (Force-Exos) or without (Ctrl-Exos), were co-cultured with human PDLCs in vitro and injected into the periodontal ligament (PDL) of rats following the establishment of RR models in vivo. Subsequently, resorption volume, PDLC pyroptotic ratio, and NLRP3-mediated pyroptosis pathway activation were performed to investigate the therapeutic effects of DFSC-Exos on PDLC pyroptosis during RR. Furthermore, the number of M1/M2 macrophages, osteoclast formation, and transwell polarization elucidated the role of Force-Exo treatment in macrophage polarization and osteoclastogenesis by inhibiting pyroptosis. Exosomal miRNA sequencing and bioinformatic analysis were used to identify differentially abundant exosome-derived miRNAs, as well as the dominant biological processes and pathways modulated by miRNA. The administration of miRNA inhibitors further verified the regulation of exosomal miRNA on RR via modulating pyroptosis. Moreover, the potential mechanisms involving candidate miRNAs and relevant pathways were explored. Results: Exosomes released by force-stimulated DFSCs (Force-Exos) inhibited NOD-like receptor 3 (NLRP3)-mediated PDLC pyroptosis, which impacted M1 macrophage activation and osteoclast formation. Based on exosomal miRNA sequencing, miR-140-3p in Force-Exos were transferred to PDLCs, and the administration of miR-140-3p inhibitors significantly reversed the reduction in PDLC pyroptosis, M1 macrophage polarization, osteoclast number, and resorption volume caused by Force-Exos. More importantly, mechanistic studies demonstrated that miR-140-3p mediated the function of Force-Exos by targeting DNA methyltransferase 1 (DNMT1) to alter the DNA methylation of suppressor of cytokine signaling (SOCS1) and the downstream nuclear factor κB (NF-κB) signaling pathway in PDLCs. Blocking the DNMT1/SOCS1/NFκB axis with DFSC-derived exosomal miR-140-3p downregulated NLRP3-mediated PDLC pyroptosis to impact M1 polarization and osteoclast formation, thereby alleviating RR. Conclusion: DFSC-Exos downregulated NLRP3-mediated PDLC pyroptosis via miR-140-3p to block DNMT1/SOCS1/NFκB axis, which impacted M1 polarization and osteoclast formation, thereby alleviating RR. [ABSTRACT FROM AUTHOR]
Copyright of Stem Cell Research & Therapy is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Human dental follicle stem cell-derived exosomes reduce root resorption by inhibiting periodontal ligament cell pyroptosis.
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  Data: <searchLink fieldCode="AR" term="%22Li%2C+Xinyi%22">Li, Xinyi</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Xinyang%22">Liu, Xinyang</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou%2C+Jianing%22">Zhou, Jianing</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Ping%22">Zhang, Ping</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Song%22">Chen, Song</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> chensong@scu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Bai%2C+Ding%22">Bai, Ding</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> baiding@scu.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Stem+Cell+Research+%26+Therapy%22">Stem Cell Research & Therapy</searchLink>. 2/21/2025, Vol. 16 Issue 1, p1-15. 15p.
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  Data: *<searchLink fieldCode="DE" term="%22SUPPRESSORS+of+cytokine+signaling%22">SUPPRESSORS of cytokine signaling</searchLink><br />*<searchLink fieldCode="DE" term="%22ROOT+resorption+%28Teeth%29%22">ROOT resorption (Teeth)</searchLink><br />*<searchLink fieldCode="DE" term="%22CYTOLOGY%22">CYTOLOGY</searchLink><br />*<searchLink fieldCode="DE" term="%22PERIODONTAL+ligament%22">PERIODONTAL ligament</searchLink><br />*<searchLink fieldCode="DE" term="%22LIFE+sciences%22">LIFE sciences</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: To explore the therapeutic effects and mechanisms of the exosomes derived from dental follicle stem cells (DFSC-Exos) in reducing osteoclastogenesis and root resorption (RR) by inhibiting periodontal ligament cell (PDLC) pyroptosis. Methods: DFSC-Exos, with force stimulation (Force-Exos) or without (Ctrl-Exos), were co-cultured with human PDLCs in vitro and injected into the periodontal ligament (PDL) of rats following the establishment of RR models in vivo. Subsequently, resorption volume, PDLC pyroptotic ratio, and NLRP3-mediated pyroptosis pathway activation were performed to investigate the therapeutic effects of DFSC-Exos on PDLC pyroptosis during RR. Furthermore, the number of M1/M2 macrophages, osteoclast formation, and transwell polarization elucidated the role of Force-Exo treatment in macrophage polarization and osteoclastogenesis by inhibiting pyroptosis. Exosomal miRNA sequencing and bioinformatic analysis were used to identify differentially abundant exosome-derived miRNAs, as well as the dominant biological processes and pathways modulated by miRNA. The administration of miRNA inhibitors further verified the regulation of exosomal miRNA on RR via modulating pyroptosis. Moreover, the potential mechanisms involving candidate miRNAs and relevant pathways were explored. Results: Exosomes released by force-stimulated DFSCs (Force-Exos) inhibited NOD-like receptor 3 (NLRP3)-mediated PDLC pyroptosis, which impacted M1 macrophage activation and osteoclast formation. Based on exosomal miRNA sequencing, miR-140-3p in Force-Exos were transferred to PDLCs, and the administration of miR-140-3p inhibitors significantly reversed the reduction in PDLC pyroptosis, M1 macrophage polarization, osteoclast number, and resorption volume caused by Force-Exos. More importantly, mechanistic studies demonstrated that miR-140-3p mediated the function of Force-Exos by targeting DNA methyltransferase 1 (DNMT1) to alter the DNA methylation of suppressor of cytokine signaling (SOCS1) and the downstream nuclear factor κB (NF-κB) signaling pathway in PDLCs. Blocking the DNMT1/SOCS1/NFκB axis with DFSC-derived exosomal miR-140-3p downregulated NLRP3-mediated PDLC pyroptosis to impact M1 polarization and osteoclast formation, thereby alleviating RR. Conclusion: DFSC-Exos downregulated NLRP3-mediated PDLC pyroptosis via miR-140-3p to block DNMT1/SOCS1/NFκB axis, which impacted M1 polarization and osteoclast formation, thereby alleviating RR. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Stem Cell Research & Therapy is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Text: English
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      – SubjectFull: ROOT resorption (Teeth)
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              Text: 2/21/2025
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