Evidence map›Paper›PMID 33111436›Full record

ArticleCell proliferation2021

Acid-sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration.

Kangcheng Zhao, Ran An, Qian Xiang, Gaocai Li, Kun Wang, Yu Song, Zhiwei Liao, Shuai Li, Wenbin Hua, Xiaobo Feng and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell proliferation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
18.4field-weighted citation impact, top 1% of its field
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

129 citing papers in PubMed, 192 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Stress-response exhaustion in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026
    Review

69 more citing papers are in PubMed but not listed here.

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

14 authors at 2 institutions in 2 countries.

Kangcheng ZhaoDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Ran AnDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Qian XiangDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Gaocai LiDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Kun WangDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yu SongDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Zhiwei LiaoDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Shuai LiDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Wenbin HuaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xiaobo FengDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xinghuo WuDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yukun ZhangDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Abhirup DasSpineLabs, St George & Sutherland Clinical School, The University of New South Wales, Sydney, NSW, Australia.
Cao YangDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.ORCID https://orcid.org/0000-0002-0058-614X
Union Hospital · CNSutherland Hospital · AU

Funding

Application Foundation and Advanced Program of Wuhan Science and Technology Bureau 2019020701011457Fundamental Research Funds for the Central Universities 2019kfyXMBZ063National Key R&D program of China 2018YFB1105700National Natural Science Foundation of China 81772401National Natural Science Foundation of China 81901977National Natural Science Foundation of China U1603121Natural Science Foundation of Hubei Province WJ2017Z016
6 · The paper itself

Abstract

objectiveLactate accumulation is an important factor in the intervertebral disc degeneration (IVDD). Currently, the effect and underlying mechanism of action of lactate on nucleus pulposus (NP) cell inflammation during IVDD are unclear. Previous studies have found that the NLRP3 inflammasome plays an important role in the regulation of NP inflammation. This study focused on the regulation of acid-sensitive ion channels (ASICs) in relation to inflammation and the effect of NLRP3 on pyroptosis levels in NP cells under acidic conditions.

designFor the in vitro experiments, human NP cells were exposed to 6 mM lactate solution; different groups were either treated with NLRP3 inhibitor or transfected with siRNA against NLRP3, siRNA against ASC or a mix of these, and mRNA and protein expression levels were then assessed. For the in vivo experiment, varying concentrations of lactate were injected into rat intervertebral discs and examined via magnetic resonance imaging (MRI) and histological staining.

resultsExtracellular lactate promoted NLRP3 inflammasome activation and degeneration of the NP extracellular matrix; furthermore, it increased the levels of inflammation and pyroptosis in the NP. Lactate-induced NLRP3 inflammasome activation was blocked by ASIC inhibitors and NLRP3 siRNA.

conclusionsExtracellular lactate regulates levels of intercellular reactive oxygen species (ROS) through ASIC1 and ASIC3. ROS activate the NF-κB signalling pathway, thus promoting NLRP3 inflammasome activation and IL-1β release, both of which promote NP degeneration.

Indexed as

PyroptosisAcid Sensing Ion ChannelsAdolescentAdultAgedCells, CulturedChildFemaleHumansInflammasomesInflammationIntervertebral Disc DegenerationMaleMiddle AgedNLR Family, Pyrin Domain-Containing 3 ProteinNucleus PulposusAcid Sensing Ion ChannelsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanacid-sensitive ion channelintervertebral disc degenerationNLRP3 inflammasomepyroptosis

Identifiers

PMID33111436
PMCPMC7791185
OpenAlexW3095754667

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.