Fig. 4

ER stress in the pathogenesis of IVDD. a Pathological changes of IVDD involved by ER stress. b The mechanisms by which ER stress promotes IVDD progression through aggravating NP degeneration. IP3R is located on ER, VDAC1 is a mitochondrial outer membrane protein, and GRP75 is a connexin, which can link IP3R to VDAC1 to form a channel for Ca²⁺ translocation. AF annulus fibrosus, AGEs advanced glycation end products, AIF apoptosis-inducing factor, CEP cartilaginous endplate, ER endoplasmic reticulum, GRP75 glucose-regulated protein 75, IP3R inositol 1,4,5-trisphosphate receptor, IVDD intervertebral disc degeneration, mSREBP mature form of SREBP1, NP nucleus pulposus, PARP poly(ADP-ribose) polymerase, RyR ryanodine receptor, SERCA sarco/endoplasmic reticulum Ca²⁺-ATPase, SREBP sterol response element binding protein, S1P site-1 membrane proteases, S2P site-2 membrane proteases, VDAC1 voltage-dependent anion-selective channel 1