Figure 2.

The failure in protein accumulation in the chondrocyte stimulates the formation of the BiP‐ GRP78 complex. This complex promotes PERK signaling to induce elf2α phosphorylation, which activates ATF‐4 to induce comprehensive apoptosis response and inhibiting protein translation. Further, BiP‐GRP78 complex mainly mediates IRE1 activation. IRE1 in this case stimulates several apoptotic signals such as RIDD that induce BiD cleavage that promotes mitochondrial‐dependent apoptosis through caspase‐3 and caspase‐9. The activation of IRE1α dependent apoptosis promotes XBPS1s that mediates proapoptosis signaling (CHOP), which enhances cell apoptosis and inhibits cell survival factors. IRE1, inositol‐requiring enzyme 1; PERK, protein kinase R‐like ER kinase; RIDD, regulated IRE1‐dependent decay