Evidence map›Paper›PMID 41518406›Full record

ArticleApoptosis : an international journal on programmed cell death2026

DDIT3 drives nucleus pulposus cell PANoptosis and intervertebral disc degeneration progression.

Kun Wang, Hangyu Ji, Jiawei Gao, Zhiqiang Wang, Yanzheng Gao, Xiaofeng Lian, Xin Peng

Abstract read
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Article in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Kun WangDepartment of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hangyu JiDepartment of Orthopedics, Zhongda Hospital, Southeast University, Nanjing, China.
Jiawei GaoMedical School of Southeast University, Nanjing, China.
Zhiqiang WangDepartment of Orthopedics, Henan Provincial People's Hospital, Peolple's Hospital of Zhengzhou University, Zhengzhou, China.
Yanzheng GaoDepartment of Orthopedics, Henan Provincial People's Hospital, Peolple's Hospital of Zhengzhou University, Zhengzhou, China. yanzhenggaohn@gs.zzu.edu.cn.
Xiaofeng LianDepartment of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lianxiaofeng@shsmu.edu.cn.
Xin PengDepartment of Orthopedics, Henan Provincial People's Hospital, Peolple's Hospital of Zhengzhou University, Zhengzhou, China. 230208983@aa.seu.edu.cn.

Funding

National Natural Science Foundation of China 82172438 and 82372473
6 · The paper itself

Abstract

Intervertebral disc degeneration (IDD) is closely linked to nucleus pulposus (NP) cell death exhibiting a PANoptotic phenotype-concurrent activation of apoptosis, necroptosis, and pyroptosis-yet its molecular regulators remain unclear. Here we identify DNA damage-inducible transcript 3 (DDIT3) as a key mediator of inflammatory PANoptosis. RNA sequencing of TNF-α-treated human NP cells revealed robust DDIT3 upregulation, consistent with observations in degenerated human discs and a rat needle-puncture IDD model. In vitro, DDIT3 knockdown (siRNA) reduced PANoptosis markers (NLRP3, caspase-1 p20, Bax, cleaved caspase-3, MLKL, p-MLKL), inflammatory cytokines (IL-1β, IL-18), and reactive oxygen species (ROS), whereas DDIT3 overexpression produced the opposite effects. Mechanistically, transcriptomics and luciferase assays indicated that DDIT3 transactivates CUL3; direct promoter binding was corroborated by chromatin immunoprecipitation and electrophoretic mobility shift assays. Molecular docking (predictive) together with co-immunoprecipitation supported a CUL3-caspase-8 interaction, and CUL3-dependent polyubiquitination enhanced caspase-8 activation. In vivo, lentiviral DDIT3 silencing mitigated disc degeneration in rat puncture models, preserved aggrecan/collagen II, and reduced PANoptotic readouts, whereas DDIT3 overexpression accelerated matrix loss. Collectively, these findings position the DDIT3-CUL3-caspase-8 axis as a central regulator of inflammatory PANoptosis in NP cells and a potential therapeutic target for halting IDD progression.

Indexed as

Intervertebral Disc DegenerationNucleus PulposusTranscription Factor CHOPAnimalsApoptosisDisease ProgressionHumansMalePyroptosisRatsRats, Sprague-DawleyTumor Necrosis Factor-alphaDDIT3 protein, humanTranscription Factor CHOPTumor Necrosis Factor-alphaCaspase-8CUL3DDIT3Intervertebral disc degenerationPANoptosisUbiquitination

Identifiers

PMID41518406

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.