Mitochondrial dysfunction triggers catabolic response in chondrocytes via ROS mediated activation of JNK/AP1 pathway.
Title
Mitochondrial dysfunction triggers catabolic response in chondrocytes via ROS mediated activation of JNK/AP1 pathway.
Creator
Ansari M Y;Ahmad N;Voleti S;Wase SJ;Novak K;Haqqi TM
Publisher
Journal of Cell Science
Date
2020
2020-10-23
Description
Mitochondrial function is impaired in osteoarthritis (OA) but its impact on cartilage catabolism is not fully understood. Here, we investigated the molecular mechanism of mitochondrial dysfunction-induced activation of catabolic response in chondrocytes. Using cartilage slices from normal and OA cartilage, we show that mitochondrial membrane potential was lower in OA cartilage which was associated with increased production of mitochondrial superoxide and catabolic genes (IL-6, COX-2, MMP-3,-9,-13 and ADAMTS5). Pharmacological induction of mitochondrial dysfunction in chondrocytes and cartilage explants using CCCP increased the mitochondrial superoxide production and the expression of IL-6, COX-2, MMP-3,-9-13 and ADAMTS5 and cartilage matrix degradation. Mitochondrial dysfunction induced expression of catabolic genes was dependent on JNK/AP1 pathway but not the NFκB pathway. Scavenging of mitochondrial superoxide with MitoTEMPO or pharmacological inhibition of JNK or cFos/cJun blocked the mitochondrial dysfunction-induced expression of the catabolic genes in chondrocytes. We demonstrate here that mitochondrial dysfunction contributes to OA pathogenesis via JNK/AP1 mediated expression of catabolic genes. Our data shows that AP1 could be used as a therapeutic target for OA management.
Subject
Inflammation; Osteoarthritis; Chondrocytes; Redox; cFos-AP1; JNK
Identifier
Format
journalArticle
URL Address
Search for Full-text
Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
ISSN
1477-9137 0021-9533
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Anatomy & Neurobiology
NEOMED Student Publications
Update Year & Number
October 2020 List
Citation
Ansari M Y;Ahmad N;Voleti S;Wase SJ;Novak K;Haqqi TM, “Mitochondrial dysfunction triggers catabolic response in chondrocytes via ROS mediated activation of JNK/AP1 pathway.,” NEOMED Bibliography Database, accessed March 18, 2024, https://neomed.omeka.net/items/show/11336.