Evidence map›Paper›PMID 34419603›Full record

ArticleOsteoarthritis and cartilage2021

TGFβ1 signaling protects chondrocytes against oxidative stress via FOXO1-autophagy axis.

I Kurakazu, Y Akasaki, H Tsushima, T Sueishi, M Toya, M Kuwahara, T Uchida, M K Lotz, Y Nakashima

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Osteoarthritis and cartilage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Forkhead box O proteins in chondrocyte aging and diseases.Journal of orthopaedic translation · 2025
    Review
  8. Article
  9. Article
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  13. Article
  14. Review
  15. Article
  16. Review
  17. Daurisoline attenuates HJournal of orthopaedic surgery and research · 2023
    Article
  18. Article
  19. Article
  20. Cartilage Homeostasis and Osteoarthritis.International journal of molecular sciences · 2022
    Review
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

9 authors at 2 institutions in 2 countries.

I KurakazuDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: kurakazu@ortho.med.kyushu-u.ac.jp.
Y AkasakiDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: akasaki@ortho.med.kyushu-u.ac.jp.
H TsushimaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: h-tsushi@ortho.med.kyushu-u.ac.jp.
T SueishiDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: takuyas@ortho.med.kyushu-u.ac.jp.
M ToyaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: mtoya@ortho.med.kyushu-u.ac.jp.
M KuwaharaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: m-kuwa@ortho.med.kyushu-u.ac.jp.
T UchidaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: t-uchida@ortho.med.kyushu-u.ac.jp.
M K LotzDepartment of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: mlotz@scripps.edu.
Y NakashimaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan. Electronic address: yasunaka@ortho.med.kyushu-u.ac.jp.
Kyushu University · JPScripps Research Institute · US

Funding

FoxO transcription factors in joint aging and osteoarthritis pathogenesisR37AG059418 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI Martin K Lotz · 2018 to 2026
$5.0M
FOXO transcription factors as critical regulators of intervertebral disc agingR01AG062533 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LOTZ, MARTIN K · 2019 to 2023
$2.0M
NIA NIH HHS R01 AG062533NIA NIH HHS R37 AG059418
6 · The paper itself

Abstract

objectiveThe forkhead box O1 (FOXO1) transcription factor is a key regulator of autophagy. In chondrocytes, reduced FOXO1 expression with aging causes osteoarthritis due to dysfunction of autophagy, but the mechanisms underlying regulation of FOXO1 expression and the reduction in expression with aging remain unclear. We investigated the mechanism by which transforming growth factor β1 (TGFβ1) signaling regulates the FOXO1-autophagy axis.

methodsExpression of FOXO1 was measured in chondrocytes after TGFβ1 treatment. Immunohistochemistry was performed to estimate the levels of activin receptor-like kinase 5 (ALK5) and FOXO1 in the knee joints of young, middle-aged and old mice. The effects of the ALK5 inhibitor and SMAD3 or SMAD2 knockdown on FOXO1 expression were evaluated. The role of TGFβ1 in autophagy after hydrogen peroxide (H

resultsTGFβ1 promoted the expression of FOXO1 mRNA and protein. Both ALK5 and FOXO1 expression decreased with aging. ALK5 inhibition and SMAD3 knockdown suppressed induction of FOXO1 expression by TGFβ1, whereas SMAD2 knockdown increased it. TGFβ1 promoted the expression of microtubule-associated proteins 1A/1B light chain 3B (LC3)-I protein via the SMAD3-FOXO1 pathway. Furthermore, under H

conclusionsTGFβ1 protects chondrocytes against oxidative stress via the FOXO1-autophagy axis, and a reduction in ALK5 expression might cause reduced FOXO1 expression with aging.

Indexed as

AgingAnimalsAutophagyCell DeathChondrocytesForkhead Box Protein O1HumansOxidative StressReceptor, Transforming Growth Factor-beta Type IRNA, MessengerSignal TransductionStifleTransforming Growth Factor beta1Forkhead Box Protein O1Foxo1 protein, mouseReceptor, Transforming Growth Factor-beta Type IRNA, MessengerTgfbr1 protein, mouseTransforming Growth Factor beta1Activin receptor-like kinase 5AutophagyForkhead box O1Oxidative stressTransforming growth factor β1

Identifiers

PMID34419603
PMCPMC8789330
OpenAlexW3194740026

What OpenQuestion holds

Textmetadata
LicenceTDM
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.