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. 2023 Nov 9;10:54. doi: 10.1186/s40779-023-00485-5

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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