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滑膜纤维化激活血管内皮细胞促进 Netrin-1 诱导的感觉神经末梢发芽并加重痛觉敏感性。

Activation of vascular endothelial cells by synovial fibrosis promotes Netrin-1-induced sensory nerve sprouting and exacerbates pain sensitivity.

机构信息

Department of Orthopaedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

J Cell Mol Med. 2023 Dec;27(23):3773-3785. doi: 10.1111/jcmm.17950. Epub 2023 Sep 13.

DOI:10.1111/jcmm.17950
PMID:37702437
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10718133/
Abstract

Synovial fibrosis is one of the most dominant histopathological changes in osteoarthritis of the knee (KOA), and activation of vascular endothelial cells in synovial fibrosis is both an important factor in mediating pain in KOA and a major contributor to the generation of pain signals. At the same time, angiogenesis and nerve fibres are more likely to underlie the pathology of pain induced by synovial fibrosis. In the present study, we established a co-culture model of human umbilical vein endothelial cells (HUVECs) with dorsal root ganglion (DRG) and detected tissue and cellular Netrin-1, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), growth-associated protein-43 (GAP43), colorectal cancer deleted (DCC), uncoordinated 5 (UNC5), and the related expression of calcitonin gene-related peptide (CGRP), substance P (SP) and nerve growth factor (NGF) in supernatant by ELISA to investigate the intervention of vascular endothelial cell activation on sensory nerve sprouting exacerbating peripheral pain sensitivity and to investigate the effect of Netrin-1 from the perspective of Netrin-1 secretion to illustrate its effector mechanism.

摘要

滑膜纤维化是膝关节骨关节炎(KOA)中最主要的组织病理学改变之一,而滑膜纤维化中血管内皮细胞的激活既是介导 KOA 疼痛的重要因素,也是产生疼痛信号的主要因素。同时,血管生成和神经纤维更可能是滑膜纤维化引起疼痛的病理基础。在本研究中,我们建立了人脐静脉内皮细胞(HUVECs)与背根神经节(DRG)的共培养模型,并通过 ELISA 检测组织和细胞中的 Netrin-1、血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)、生长相关蛋白-43(GAP43)、结直肠癌缺失(DCC)、Uncoordinated 5(UNC5)以及相关表达的降钙素基因相关肽(CGRP)、P 物质(SP)和神经生长因子(NGF)在上清液中的表达,以探讨血管内皮细胞激活对感觉神经末梢发芽加剧周围痛觉敏感性的干预作用,并从 Netrin-1 分泌的角度探讨 Netrin-1 的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/509aa1da7a35/JCMM-27-3773-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/358b865eab78/JCMM-27-3773-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/297ec7318320/JCMM-27-3773-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/9034f7877bdc/JCMM-27-3773-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/bd4a9b7b1742/JCMM-27-3773-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/6d61e7c25e3e/JCMM-27-3773-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/509aa1da7a35/JCMM-27-3773-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/358b865eab78/JCMM-27-3773-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/297ec7318320/JCMM-27-3773-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/9034f7877bdc/JCMM-27-3773-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/bd4a9b7b1742/JCMM-27-3773-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/6d61e7c25e3e/JCMM-27-3773-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8a/10718133/509aa1da7a35/JCMM-27-3773-g006.jpg

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