Impact of Chondrocyte Inflammation on Glial Cell Activation: The Mediating Role of Nitric Oxide.

IF 2.7 4区医学 Q1 ORTHOPEDICS CARTILAGE Pub Date : 2024-10-29 DOI:10.1177/19476035241292323

Mariam Farrag, Alfonso Cordero-Barreal, Djedjiga Ait Eldjoudi, María Varela-García, Carlos Torrijos Pulpón, Francisca Lago, Amina Essawy, Ahmed Soffar, Jesus Pino, Yousof Farrag, Oreste Gualillo

{"title":"Impact of Chondrocyte Inflammation on Glial Cell Activation: The Mediating Role of Nitric Oxide.","authors":"Mariam Farrag, Alfonso Cordero-Barreal, Djedjiga Ait Eldjoudi, María Varela-García, Carlos Torrijos Pulpón, Francisca Lago, Amina Essawy, Ahmed Soffar, Jesus Pino, Yousof Farrag, Oreste Gualillo","doi":"10.1177/19476035241292323","DOIUrl":null,"url":null,"abstract":"Objective: This study investigates how the inflammatory response of ATDC5 murine chondrogenic cells influences the activity of C6 (rat) and GL261 (mouse) glial cell lines. Prior research suggested nitric oxide (NO) involvement in cartilage-immune crosstalk. The current study explores whether NO, produced by inflamed chondrocytes, mediates signaling between chondrocytes and glial cells.Design: Pre-challenged ATDC5 cells with 250 ng/ml of lipopolysaccharide (LPS) were cocultured with GL261 or C6 glioma cells for 24 h with a transwell culture system. Cell viability was assessed using MTT assay. Gene and protein expression were evaluated by qRT-PCR and WB, respectively.Results: Real-time reverse transcription-polymerase chain reaction (RT-qPCR) indicated statistically significant upregulation of LCN2, IL-6, TNF-α, IL-1β, and GFAP in glial cells following 24-h coculture with challenged ATDC5 cells. Suppression of LPS-induced NO production by aminoguanidine decreased LPS-mediated LCN2 and IL-6 expression in glioma cells. We identified also the involvement of the ERK1/2 and AKT signaling pathways in the glial neuroinflammatory response.Conclusions: This study demonstrates, for the first time, that NO produced by inflamed murine chondrocytes mediated pro-inflammatory responses in glial cells via ERK1/2 and AKT signaling, highlighting a potential mechanism linking cartilage NO to neuroinflammation and chronic pain in osteoarthritis.","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556648/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CARTILAGE","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/19476035241292323","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: This study investigates how the inflammatory response of ATDC5 murine chondrogenic cells influences the activity of C6 (rat) and GL261 (mouse) glial cell lines. Prior research suggested nitric oxide (NO) involvement in cartilage-immune crosstalk. The current study explores whether NO, produced by inflamed chondrocytes, mediates signaling between chondrocytes and glial cells.

Design: Pre-challenged ATDC5 cells with 250 ng/ml of lipopolysaccharide (LPS) were cocultured with GL261 or C6 glioma cells for 24 h with a transwell culture system. Cell viability was assessed using MTT assay. Gene and protein expression were evaluated by qRT-PCR and WB, respectively.

Results: Real-time reverse transcription-polymerase chain reaction (RT-qPCR) indicated statistically significant upregulation of LCN2, IL-6, TNF-α, IL-1β, and GFAP in glial cells following 24-h coculture with challenged ATDC5 cells. Suppression of LPS-induced NO production by aminoguanidine decreased LPS-mediated LCN2 and IL-6 expression in glioma cells. We identified also the involvement of the ERK1/2 and AKT signaling pathways in the glial neuroinflammatory response.

Conclusions: This study demonstrates, for the first time, that NO produced by inflamed murine chondrocytes mediated pro-inflammatory responses in glial cells via ERK1/2 and AKT signaling, highlighting a potential mechanism linking cartilage NO to neuroinflammation and chronic pain in osteoarthritis.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

软骨细胞炎症对神经胶质细胞活化的影响：一氧化氮的中介作用

研究目的本研究探讨了 ATDC5 小鼠软骨细胞的炎症反应如何影响 C6（大鼠）和 GL261（小鼠）神经胶质细胞系的活性。先前的研究表明，一氧化氮（NO）参与了软骨-免疫串扰。本研究探讨了发炎的软骨细胞产生的一氧化氮是否会介导软骨细胞和神经胶质细胞之间的信号传递：设计：用 250 纳克/毫升的脂多糖（LPS）预拮抗 ATDC5 细胞，与 GL261 或 C6 胶质瘤细胞共培养 24 小时。用 MTT 法评估细胞活力。基因和蛋白质表达分别通过 qRT-PCR 和 WB 进行评估：结果：实时逆转录聚合酶链反应（RT-qPCR）表明，与受到挑战的 ATDC5 细胞共培养 24 小时后，胶质细胞中 LCN2、IL-6、TNF-α、IL-1β 和 GFAP 的上调具有统计学意义。氨基胍抑制 LPS 诱导的 NO 生成，降低了 LPS 介导的 LCN2 和 IL-6 在胶质瘤细胞中的表达。我们还发现ERK1/2和AKT信号通路参与了胶质神经炎症反应：本研究首次证明，发炎的小鼠软骨细胞产生的 NO 可通过 ERK1/2 和 AKT 信号传导介导神经胶质细胞的促炎反应，这凸显了软骨 NO 与骨关节炎的神经炎症和慢性疼痛之间的潜在联系机制。

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分钟内获得全文去求助

来源期刊

CARTILAGE ORTHOPEDICS-

CiteScore

6.90

自引率

7.10%

发文量

期刊介绍： CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair. The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers. The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.