Fig 6. Model of palmitate-induced ER stress and chondrocyte apoptosis in mouse knee joints.
Dietary palmitate induces ER stress in mouse knee joints. Under ER stress, BIP is released from IRE1 to trigger activation of IRE1 via autophosphorylation (P-IRE1) which further activates the expression of XBP1. Similarly, PERK is autophosphorylated (P-PERK) following the release of BIP thus inducing the ATF4 expression. Both XBP1 and ATF4 induce CHOP expression which further induces the expression of Nupr1 to elicit CC3-mediated chondrocyte apoptosis. Both CHOP and Nupr1 could induce TRB3 expression to inhibit chondrocyte survival. →, single-step stimulation;, putative single-step stimulation; → →, multistep stimulations; ⊥ ⊥, multistep inhibitions.