YAP1 exacerbates pyroptosis and senescence in nucleus pulposus cells by promoting BNIP3-mediated mitophagy

Peng, Xin; Ji, Hang-Yu; Gao, Jia-Wei; Hong, Shang-hao; Zhang, Tong; Yang, Guang; Wu, Xiaotao; Gao, Yanzheng; Wang, Kun

doi:10.1016/j.intimp.2024.113434

International Immunopharmacology

2024

DOI: 10.1016/j.intimp.2024.113434

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YAP1 exacerbates pyroptosis and senescence in nucleus pulposus cells by promoting BNIP3-mediated mitophagy

Xin Peng,

Hang-Yu Ji,

Jia-Wei Gao

et al.

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2024

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Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway

Li,

Cheng,

et al. 2024

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Purpose Intervertebral disc degeneration (IDD) is a leading cause of low back pain, and developing new molecular drugs and targets for IDD is a new direction for future treatment strategies. The aim of this study is to investigate the effects and mechanisms of tomatidine in ameliorating lumbar IDD. Methods Nucleus pulposus cells (NPCs) exposed to lipopolysaccharides were used as an in vitro model to investigate changes in the expression of extracellular matrix components and associated signaling pathway molecules. A lumbar instability model was used to simulate IDD. Tomatidine (Td) was then administered intraperitoneally, and its effects were evaluated through histopathological analysis. Results In vitro, Td significantly promoted ECM anabolism, inhibited ECM catabolism, and reduced oxidative stress and ferroptosis in LPS-stimulated NPCs. When Nrf2 expression was inhibited, oxidative stress and ferroptosis were exacerbated, and the protective effects of Td on NPCs were lost, suggesting the Nrf2/HO-1/GPX4 axis is critical for the therapeutic effects of Td. In vivo, histopathological analysis demonstrated that Td ameliorated IDD in a murine model. Conclusion Td alleviates IDD in vitro and in vivo by activating the Nrf2/HO-1/GPX4 pathway to inhibit ferroptosis in NPCs. This mechanism suggests Td is a promising candidate for IDD treatment.

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Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway

Li,

Cheng,

et al. 2024

DDDT

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show abstract

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YAP1 exacerbates pyroptosis and senescence in nucleus pulposus cells by promoting BNIP3-mediated mitophagy

Cited by 1 publication

References 47 publications

Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway

Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway

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