Effects of cyclooxygenase and soluble epoxide hydrolase inhibitors on apoptosis of cultured primary equine chondrocytes

Apoptosis is an important mechanism underlying chondrocyte loss in osteoarthritis that could be affected by modulation of lipid signaling via inhibition of cyclooxygenases (COX) and soluble epoxide hydrolase (sEH).To determine the impact of inhibiting COX and sEH alone or in combination on apoptosis of equine chondrocytes.Cultured primary equine chondrocytes were subjected to serum deprivation or incubation with 1 μg/ml tunicamycin for 24 h to induce apoptosis via caspase activation and endoplasmic reticulum (ER) stress, respectively. Cells were treated with the non-selective COX inhibitor phenylbutazone, the COX-2 selective inhibitor firocoxib and the sEH inhibitor t-TUCB alone or in combination. The inhibitors were used at half-maximal (ICIn the caspase model, 10xICIn vitro findings that will need to be verified in vivo.Chondrocyte apoptosis caused by ER stress can be enhanced by COX inhibition but prevented by concurrent inhibition of sEH.