Chondrocyte AMP-activated protein kinase (AMPK) activity modulates the unfolded protein response (UPR) and completes the model illustrated here. (A) Primary bovine-knee chondrocytes embedded in alginate were pre-treated with activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (1 mM) for 24 hours before being subjected to mechanical injury as described (Methods). Expression of 78-kDa glucose-regulated protein (GRP78) and C/EBP Binding protein (CHOP) was examined by western blot. Data are representative of three individual experiments. (B) In this model, biomechanical injury induces decreased AMPKα activity (via dephosphorylation) and also induces CHOP expression in chondrocytes. AMPK activity limits CHOP expression. Conversely, induction of decrease in AMPK activity plays a major role in the capacity of IL-1β to induce CHOP expression. CHOP mediates oxidative stress and apoptosis in chondrocytes. CHOP also potentiates the capacity of IL-1β to promote certain pro-catabolic responses in chondrocytes.