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

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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 October 25, 2021, https://neomed.omeka.net/items/show/11336.

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