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

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.