Pranoprofen inhibits endoplasmic reticulum stress-mediated apoptosis of chondrocytes.

Abstract

Background: Endoplasmic reticulum stress (ERS) is a newly discovered pathway that causes apoptosis. At present, there is little research about the non-steroidal anti-inflammatory drug (NSAID) on the apoptosis of chondrocytes CHs. Our study aimed to test the anti-apoptosis effects of pranoprofen (PF), a specific prostaglandin E2 (PGE2) inhibitor, on human CHs.

Methods: We firstly made a distinguish about the levels of PGE2, ERS, and apoptosis between cartilage with and without OA. Then CHs isolated from healthy cartilage were pretreated H2O2 or tunicamycin (TM) to activate ERS, and then exposed to PF. Expression of type II collagen, Runx-2, COX-9, SOD1, GPX1, GRP78, CHOP, caspase-12, ROS level, and apoptosis cell ratio was determined by immunofluorescence, Western blot, RT-PCR, or flow cytometry respectively.

Results: We found that oxidative stress, PGE2, ERS, and apoptosis were upregulated in OA cartilage. In addition, H2O2 and TM could increase the levels of PGE2, GRP78, CHOP, caspase-12, and reactive oxygen species (ROS), resulting in the degeneration of CHs. PF significantly reduced the expression of PGE2 and suppressed the ERS and apoptosis caused by H2O2 and TM, showing a protective function of CHs degeneration.

Conclusions: This study demonstrates the anti-apoptotic effect of PF in the abrogation of the ERS-mediated apoptosis in human CHs, suggesting a new mechanism of PF in the treatment of OA.