Evidence map›Paper›PMID 36945021›Full record

ArticleArthritis research & therapy2023

TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo.

Kun Wang, Dengbo Yao, Yuxi Li, Ming Li, Weike Zeng, Zhuangyao Liao, Engming Chen, Shixin Lu, Kaihui Su, Zhen Che and 3 more

Open access · goldFull text read
In one paragraph

Article in Arthritis research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.6field-weighted citation impact, top 8% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

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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

13 authors at 2 institutions in 1 country.

Kun Wang *Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Dengbo Yao *Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Yuxi Li *Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Ming LiDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Weike ZengDepartment of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Zhuangyao LiaoDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Engming ChenDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Shixin LuDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Kaihui SuDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Zhen CheDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Yuwei LiangDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
Peng WangDepartment of Orthopedics, Eighth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, 3025 Shennan Middle Road, Shenzhen, 518033, China. wangp57@mail.sysu.edu.cn.
Lin HuangDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China. huangl5@mail.sysu.edu.cn.
Sun Yat-sen University · CNNanchang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of the p38 inhibitor TAK-715 in intervertebral disc degeneration.

methodsNPCs were treated with IL-1β to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines (HMGB1), and ECM components (collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration.

resultsIL-1β-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1β-induced inflammatory mediator production (COX-2) and inflammatory cytokine production (HMGB1) and degraded the ECM (collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations.

conclusionTAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD.

Indexed as

ApoptosisBenzamidesExtracellular MatrixIntervertebral Disc DegenerationNucleus PulposusAnimalsCyclooxygenase 2HMGB1 ProteinInterleukin-1betaIntervertebral DiscMatrix Metalloproteinase 3Matrix Metalloproteinase 9RatsThiazolesBenzamidesCyclooxygenase 2HMGB1 ProteinInterleukin-1betaMatrix Metalloproteinase 3Matrix Metalloproteinase 9N-(4-(2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl)-2-pyridyl)benzamideThiazolesApoptosisIDDInflammationIntervertebral disc degenerationp38MAPKTAK-715

Identifiers

PMID36945021
PMCPMC10029231
OpenAlexW4328129061

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read55
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 Socratic graph.