Table 1.

Mechanism and intervention methods of ferroptosis in IVDD.

Study	Induction of ferroptosis	Mechanism	Effects on cells	Intervention method
Zhang et al. (44)	Hcy to simulate the pathological condition of HHcy	Promotion of methylase expression and the upregulation of the GPX4 methylation.	Inducing ferroptosis in NPCs	Folic acid reducing the ability of HHcy to promote IVDD
Bin et al. (45)	IL-6 to simulate inflammatory condition	IL-6/miR-10a-5p/IL-6R axis	Inducing ferroptosis in cartilage cells	Inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway
Lu et al. (71)	TBHP to simulate oxidative stress condition	FPN downregulation and intercellular iron overload	Inducing ferroptosis in NPCs.	Enhancing the nuclear translocation of MTF1 by suppressing the JNK pathway and ameliorating the progression of IVDD
Shan et al. (31)	Heme to simulate neovascularization condition	Increased heme catabolism, downregulation of GPX4, and intercellular iron overload, which might be mediated by the Notch pathway	Inducing ferroptosis in NPCs.	Inhibiting of the Notch signaling pathway
Yang et al. (72)	TBHP to simulate oxidative stress condition	NCOA4-mediated ferritinophagy and intercellular iron overload	Inducing ferroptosis in NPCs and AFCs.	Silencing NCOA4 to alleviate ferroptosis
Li et al. (114)	TBHP to simulate oxidative stress condition	Upregulation of ATF3 and ROS products	Inducing ferroptosis in NPCs.	Silencing ATF3 by miR-874-3p and alleviating IVDD
Wang et al. (115)	FAC to simulate iron overload condition	Mineralization of endplate chondrocytes and oxidative stress	Inducing ferroptosis in endplate chondrocytes.	DFO, NAC and ferrostatin-1 rescuing high dose iron-induced IVDD and cartilage endplate calcification
Yu et al. (116)	IL-1β to simulate inflammatory condition	Decreased NRF2 expression and upregulation of ROS products	Inducing ferroptosis in NPCs.	circ_0072464 shuttled by BMSC-secreted EVs inhibiting NPC ferroptosis by downregulation of miR-431 and upregulation of NRF2.

IVDD, Intervertebral disc degeneration; Hcy, homocysteine; HHcy, hyperhomocysteinemia; NPCs, nucleus pulposus cells; TBHP, tert-butyl hydroperoxide; FPN, ferroportin; MTF1, metal-regulatory transcription factor 1; GPX4, glutathione peroxidase 4; NCOA4, nuclear receptor coactivator 4; AFCs, annulus fibrosus cells; ATF3, activation transcription factor 3; ROS, reactive oxygen species; FAC, ferric ammonium citrate; DFO, deferoxamine; NAC, N-acetyl-cysteine; NRF2, nuclear factor-erythroid 2 like 2; BMSC, bone marrow mesenchymal stem cells; EV, extracellular vesicle.