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EphrinB2 介导体细胞自噬通过破坏软骨内稳态引发创伤性关节炎。

EphrinB2-mediated chondrocyte autophagy induces post-traumatic arthritis via rupture of cartilage homeostasis.

机构信息

Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.

The Second Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

J Cell Mol Med. 2024 Sep;28(18):e70095. doi: 10.1111/jcmm.70095.

DOI:10.1111/jcmm.70095
PMID:39289794
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11408268/
Abstract

EphrinB2, a member of the Ephrin family, has been linked to several orthopaedic conditions. Nevertheless, the correlation between ephrinB2 and post-traumatic arthritis (PTOA) remains unclear. Human PTOA cartilage from human and mouse knee joints was systematically analysed to investigate the relationship between EphrinB2 and PTOA using SO-FG and toluidine blue staining, micro-CT, histomorphometry, immunohistochemistry, immunofluorescence, lentiviral articular injection and in situ end labeling (TUNEL) assays. EphrinB2 expression was significantly downregulated in PTOA chondrocytes. Blocking EphrinB2 increased the breakdown of cartilage matrix in mice with PTOA via reducing the process of chondrocyte autophagy. The presence of severe cartilage damage was evident, as indicated by a considerable decrease in both cartilage thickness and area, accompanied by an increase in chondrocyte death. Altogether, EphrinB2 is required for the maintenance of cartilage homeostasis in post-traumatic arthritis, and EphrinB2 ablation is associated with accelerated chondrocyte matrix degeneration, finally causing damage to the articular cartilage.

摘要

EphrinB2 是 Ephrin 家族的一员,与多种骨科疾病有关。然而,EphrinB2 与创伤后关节炎(PTOA)之间的相关性尚不清楚。我们系统地分析了来自人膝关节和小鼠膝关节的人 PTOA 软骨,使用 SO-FG 和甲苯胺蓝染色、micro-CT、组织形态计量学、免疫组织化学、免疫荧光、慢病毒关节内注射和原位末端标记(TUNEL)检测,研究 EphrinB2 与 PTOA 之间的关系。在 PTOA 软骨细胞中 EphrinB2 的表达明显下调。阻断 EphrinB2 通过减少软骨细胞自噬过程,增加了 PTOA 小鼠软骨基质的破坏。严重的软骨损伤明显存在,软骨厚度和面积明显减少,同时软骨细胞死亡增加。总之,EphrinB2 是维持创伤后关节炎软骨内稳态所必需的,EphrinB2 缺失与软骨细胞基质退化加速有关,最终导致关节软骨损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/252cb17ac5a1/JCMM-28-e70095-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/4bc0cd5f8c91/JCMM-28-e70095-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/97f59deb875f/JCMM-28-e70095-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/e7a8e166c0c0/JCMM-28-e70095-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/5712c7756e71/JCMM-28-e70095-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/252cb17ac5a1/JCMM-28-e70095-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/4bc0cd5f8c91/JCMM-28-e70095-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/97f59deb875f/JCMM-28-e70095-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/e7a8e166c0c0/JCMM-28-e70095-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/5712c7756e71/JCMM-28-e70095-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/000e/11408268/252cb17ac5a1/JCMM-28-e70095-g004.jpg

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