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痤疮丙酸杆菌通过 TLR2/JNK/线粒体介导的途径促进髓核细胞凋亡诱导椎间盘退变。

Propionibacterium acnes induces intervertebral disc degeneration by promoting nucleus pulposus cell apoptosis via the TLR2/JNK/mitochondrial-mediated pathway.

机构信息

Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200000, China.

Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200000, China.

出版信息

Emerg Microbes Infect. 2018 Jan 10;7(1):1. doi: 10.1038/s41426-017-0002-0.

Abstract

Evidence suggests that intervertebral disc degeneration (IVDD) can be induced by Propionibacterium acnes (P. acnes), although the underlying mechanisms are unclear. In this study, we analyzed the pathological changes in degenerated human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative samples, P. acnes-positive IVDs showed increased apoptosis of nucleus pulposus cells (NPCs) concomitant with severe IVDD. Then, a P. acnes-inoculated IVD animal model was established, and severe IVDD was induced by P. acnes infection by promoting NPC apoptosis. The results suggested that P.acnes-induced apoptosis of NPCs via the Toll-like receptor 2 (TLR2)/c-Jun N-terminal kinase (JNK) pathway and mitochondrial-mediated cell death. In addition, P. acnes was found to activate autophagy, which likely plays a role in apoptosis of NPCs. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced apoptosis of NPCs via the TLR2/JNK pathway is likely responsible for the pathology of IVDD.

摘要

有证据表明痤疮丙酸杆菌(P. acnes)可引起椎间盘退变(IVDD),但其潜在机制尚不清楚。在本研究中,我们分析了感染 P. acnes 的退变人椎间盘(IVD)的病理变化。与 P. acnes 阴性样本相比,P. acnes 阳性 IVD 显示髓核细胞(NPC)凋亡增加,同时伴有严重的 IVDD。然后,建立了 P. acnes 接种的 IVD 动物模型,通过促进 NPC 凋亡,P. acnes 感染可诱导严重的 IVDD。结果表明,P.acnes 通过 Toll 样受体 2(TLR2)/c-Jun N-末端激酶(JNK)途径和线粒体介导的细胞死亡诱导 NPC 凋亡。此外,发现 P. acnes 可激活自噬,这可能在 NPC 凋亡中起作用。总的来说,这些发现进一步验证了 P. acnes 参与 IVDD 病理学的作用,并提供了证据表明,P. acnes 通过 TLR2/JNK 途径诱导 NPC 凋亡可能是 IVDD 病理学的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08c/5837142/e8eeeb2df795/41426_2017_2_Fig1_HTML.jpg

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