Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis.
Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis.
复制标题
牙周膜干细胞焦亡引发的牙周炎症加剧牙周炎
DOI：
10.3389/fcell.2021.663037
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zou D
中科院分区：
文献类型：
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作者：
Chen Q;Liu X;Wang D;Zheng J;Chen L;Xie Q;Liu X;Niu S;Qu G;Lan J;Li J;Yang C;Zou D
牙周炎是一种免疫性炎症性疾病，可导致骨和结缔组织的进行性破坏，并伴有牙周膜干细胞（PDLSCs）功能障碍甚至丧失。gasdermin-D介导的细胞凋亡（GSDMD）参与炎症性疾病的发病机制。然而，焦亡是否介导PDLSC损失，以及焦亡引发的炎症是否参与牙周炎的病理进展仍不清楚。在此，我们发现PDLSCs在人类牙周炎期间遭受GSDMD依赖的焦亡以释放白细胞介素-1 β（IL-1β）。龈沟液中IL-1β水平的升高与牙周炎的严重程度显著相关。牙周细菌和细胞质脂多糖（LPS）引起的caspase-4/GSDMD介导的焦亡是导致PDLSC丢失的主要原因。PDLSCs通过向组织微环境中释放IL-1β，抑制成骨细胞的生成，促进破骨细胞的生成，加重牙周炎的病理损伤。在大鼠牙周炎模型中，药物抑制caspase-4或IL-1β抗体阻断导致牙槽骨丢失和牙周膜损伤显著减少。此外，Gsdmd缺乏减轻小鼠实验性牙周炎的牙周炎症和骨丢失。这些结果表明，GSDMD驱动的PDLSC焦亡和丢失通过增加IL-1β释放、增强炎症和促进破骨细胞生成在牙周炎的发病机制中起关键作用。
Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory diseases. However, whether pyroptosis mediates PDLSC loss, and inflammation triggered by pyroptosis is involved in the pathological progression of periodontitis remain unclear. Here, we found that PDLSCs suffered GSDMD-dependent pyroptosis to release interleukin-1β (IL-1β) during human periodontitis. Importantly, the increased IL-1β level in gingival crevicular fluid was significantly correlated with periodontitis severity. The caspase-4/GSDMD-mediated pyroptosis caused by periodontal bacteria and cytoplasmic lipopolysaccharide (LPS) dominantly contributed to PDLSC loss. By releasing IL-1β into the tissue microenvironment, pyroptotic PDLSCs inhibited osteoblastogenesis and promoted osteoclastogenesis, which exacerbated the pathological damage of periodontitis. Pharmacological inhibition of caspase-4 or IL-1β antibody blockade in a rat periodontitis model lead to the significantly reduced loss of alveolar bone and periodontal ligament damage. Furthermore, Gsdmd deficiency alleviated periodontal inflammation and bone loss in mouse experimental periodontitis. These findings indicate that GSDMD-driven PDLSC pyroptosis and loss plays a pivotal role in the pathogenesis of periodontitis by increasing IL-1β release, enhancing inflammation, and promoting osteoclastogenesis.
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影响因子：
3.8
作者：
Lilia Garcia-Hernandez, Ana;Enrique Munoz-Saavedra, Angel;Rubio-Infante, Nestor
通讯作者：
Rubio-Infante, Nestor
影响因子：
64.8
作者：
Ding, Jingjin;Wang, Kun;Shao, Feng
通讯作者：
Shao, Feng
DOI：
10.1007/978-1-4939-9012-2_7
发表时间：
2019-01-01
期刊：
ODONTOGENESIS
影响因子：
--
作者：
Al-Habib, Mey;Huang, George T. -J.
通讯作者：
Huang, George T. -J.
影响因子：
9.7
作者：
Bhattarai, Govinda;Poudel, Sher Bahadur;Lee, Jeong-Chae
通讯作者：
Lee, Jeong-Chae
焦亡是由非选择性gasdermin-D孔驱动的，其形态与MLKL通道介导的坏死性凋亡不同
影响因子：
44.1
作者：
通讯作者：
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