Pioglitazone inhibits advanced glycation end product-induced TNF-α and MMP-13 expression via the antagonism of NF-κB activation in chondrocytes.

Abstract:

OBJECTIVE:Advanced glycation end products (AGEs) play a pivotal role in the initiation and progression of osteoarthritis (OA). Peroxisome proliferator-activated receptor-γ (PPARγ) has been shown to exhibit anti-inflammatory and anticatabolic properties and to be protective in animal models of OA. This study was aimed to investigate the possible protective effect of the PPARγ agonist pioglitazone on AGE-induced chondrocyte damage. METHODS:Cultured chondrocytes were stimulated with AGEs in the presence or absence of an antibody against the receptor for AGEs (anti-RAGE), an inhibitor of NF-κB (pyrrolidine dithiocarbamate) and pioglitazone. The RNA expression levels of TNF-α, matrix metalloproteinase (MMP)-13 and PPARγ were detected by RT-PCR. The expression of nuclear p65 was determined by Western blot analysis. RESULTS:Upregulation of TNF-α and MMP-13 as well as downregulation of PPARγ were induced by AGEs in a time- and dose-dependent manner. The maximum effect was induced by 100 μg/ml AGEs. This effect can be inhibited by anti-RAGE. Pioglitazone dose-dependently inhibited the expression of TNF-α and MMP-13 induced by AGEs, which was combined with the inhibition of nuclear p65 expression. CONCLUSION:The PPARγ agonist pioglitazone modulates TNF-α and MMP-13 expression in cultured rabbit chondrocytes via NF-κB signaling. It indicates that pioglitazone may have therapeutic potential in OA.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Chen C,Ma C,Zhang Y,Zeng Y,Li Y,Wang W

doi

10.1159/000369074

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

265-72

issue

5-6

eissn

0031-7012

issn

1423-0313

pii

000369074

journal_volume

94

pub_type

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