Figure 6

Effect of sodium ferulate on caspase cascade apoptosis and IKK/NF-κB pathways induced by TNF/TNF receptor. Combination of TNF and TNF receptor (TNFR) on the cell membrane will activate two downstream signal pathways. One is the caspase cascade apoptosis pathway, which recruits TNF receptor-associated death domain (TRADD), Fas-associated death domain protein (FADD) and death domain (DD) and forms death inducing signaling complex (DISC), the initiator caspases (caspase-8), and activates executioner caspases (caspase-3). Active executioner caspases cleave the death substrates, eventually resulting in apoptosis. The other is the inhibitor of NF-κB kinase (IKK)/NF-κB pathway, which activates the cytoplasmic IKK. Phosphorylated IKK (p-IKK) activates NF-κB inhibitor, alpha (IκBα) into the phosphorylation phase. Phosphorylated IκBα is then ubiquitinated and degraded by the proteasome and active NF-κB is released. NF-κB translocates to the nucleus, where it activates proinflammatory and pro-apoptotic gene production. In rat OA chondrocytes, sodium ferulate (SF) inhibited both the caspase cascade apoptosis pathway and the IKK/NF-κB pathway induced by combination of TNF/TNFR. COX-2, cyclooxygenase-2; NO, nitric oxide; PGE2, prostaglandin E₂; TRAF, TNF receptor-associated factor.