Issue 3, 2016

DUSP19, a downstream effector of leptin, inhibits chondrocyte apoptosis via dephosphorylating JNK during osteoarthritis pathogenesis

Abstract

Increased mitogen-activated protein kinase (MAPK) activity has been found in human osteoarthritis (OA). Dual specificity protein phosphatase 19 (DUSP19), a member of mitogen-activated protein kinase (MAPK) phosphatases (MKPs), controls the activity of various MAPKs. This study was aimed to explore the function of DUSP19 during OA pathogenesis. Here, OA and healthy control data were downloaded from the NCBI Gene Expression Omnibus database (GSE57218). Forty-five patients with OA and 25 healthy donors were enrolled in this study. A rat OA model was induced by anterior cruciate ligament transection. Primary cultured chondrocytes were treated with leptin (10 ng mL−1). Cell survival, cell apoptosis and reactive oxygen species (ROS) were identified by CCK-8 and flow cytometry, respectively. In the cartilage of OA patients, DUSP19 was expressed in a lower level than in the cartilage of healthy control. The DUSP19 level was negatively correlated with leptin, which was confirmed by experiments in the rat OA model. Moreover, cell apoptosis and JNK activation in the rat cartilage were increased with the increasing of leptin levels and the decreasing of DUSP19 mRNA levels. In primary culture chondrocytes, exogenous leptin suppressed DUSP19 expression. The ectopic expression of DUSP19 significantly ameliorated leptin-induced apoptosis in damaged chondrocytes, accompanied by the reduced production of ROS. Moreover, the activity of JNK stimulated by leptin was suppressed by DUSP19 overexpression. The present study indicated that DUSP19, a downstream of leptin, inhibited apoptosis of chondrocytes through dephosphorylating JNK.

Graphical abstract: DUSP19, a downstream effector of leptin, inhibits chondrocyte apoptosis via dephosphorylating JNK during osteoarthritis pathogenesis

Article information

Article type
Paper
Submitted
12 Nov 2015
Accepted
16 Dec 2015
First published
11 Jan 2016

Mol. BioSyst., 2016,12, 721-728

DUSP19, a downstream effector of leptin, inhibits chondrocyte apoptosis via dephosphorylating JNK during osteoarthritis pathogenesis

Y. Wang, Z. Xu, J. Wang and S. Xu, Mol. BioSyst., 2016, 12, 721 DOI: 10.1039/C5MB00776C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements