Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics.

Journal of dental research Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI:10.1177/00220345241262706
H Liu, Y Zhang, Y Zhang, Y Huang, Y Yang, Y Zhao, S Chen, J Deng, W Li, B Han
{"title":"Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics.","authors":"H Liu, Y Zhang, Y Zhang, Y Huang, Y Yang, Y Zhao, S Chen, J Deng, W Li, B Han","doi":"10.1177/00220345241262706","DOIUrl":null,"url":null,"abstract":"<p><p>Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force-guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell-derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force-activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of dental research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/00220345241262706","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/5 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force-guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell-derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force-activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.

牙周韧带细胞凋亡激活正畸中的 Lepr+ 骨生成器
牙槽骨(AB)重塑,包括形成和吸收,是正畸牙齿移动(OTM)的基础。然而,新骨形成的来源和机制仍不清楚。因此,我们以瘦素受体+(Lepr+)成骨细胞和牙周韧带细胞(PDLCs)为重点,旨在了解 OTM 期间骨形成的潜在机制。我们证明,在正畸骨再生过程中,由力诱导的 PDLC 细胞凋亡激活的 Lepr+ 细胞是一种独特的骨生成细胞。我们研究了体内和体外的骨形成。单细胞RNA测序分析和系谱追踪表明,Lepr代表了在OTM过程中被激活并分化成成骨细胞的干细胞亚群。在小鼠模型中靶向消融 Lepr+ 细胞会破坏正畸力引导的骨再生。此外,细胞凋亡和连续荧光标记实验显示,PDLCs 的凋亡先于新骨沉积。我们发现,PDL干细胞衍生的凋亡囊泡在体外激活了Lepr+细胞。抑制细胞凋亡后,正畸力激活的造骨细胞和成骨作用明显降低。值得注意的是,我们发现在 OTM 过程中,骨形成发生在受压侧;这在本文中是首次报道。总之,我们发现了 OTM 期间骨形成的潜在机制,这可能会为 AB 再生提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信