Evidence map›Paper›PMID 33731712›Full record

ArticleNature communications2021

Mechanical stress determines the configuration of TGFβ activation in articular cartilage.

Gehua Zhen, Qiaoyue Guo, Yusheng Li, Chuanlong Wu, Shouan Zhu, Ruomei Wang, X Edward Guo, Byoung Choul Kim, Jessie Huang, Yizhong Hu and 5 more

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

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
20.4field-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

111 citing papers in PubMed, 172 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Lower TG/HDL-C ratio is associated with increased severity of spinal deformity.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Gehua ZhenDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Qiaoyue GuoDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Yusheng LiDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Chuanlong WuDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Shouan ZhuDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Ruomei WangDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
X Edward GuoDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Byoung Choul KimDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0001-5101-4339
Jessie HuangDepartment of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ, USA.
Yizhong HuDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Yang DanDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
Mei WanDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0001-9404-540X
Taekjip HaDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-2195-6258
Steven AnDepartment of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ, USA.ORCID 0000-0003-4723-1888
Xu CaoDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA. xcao11@jhmi.edu.ORCID 0000-0001-8614-6059
Johns Hopkins University · USColumbia University · USRutgers, The State University of New Jersey · US

Funding

Skeleton and Joint Degeneration with AgingP01AG066603 · NIA · JOHNS HOPKINS UNIVERSITY · PI CAO, XU · 2021 to 2025
$9.2M
Subchondral Bone Cavities in Osteoarthritis PainRF1AG068997 · NIA · JOHNS HOPKINS UNIVERSITY · PI CAO, XU, GUAN, YUN · 2020 to 2020
$2.5M
TGF-beta Activity in the Subchondral Bone and Onset of OAR01AR063943 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CAO, XU · 2013 to 2017
$2.2M
Subchondral Bone Cavities in Osteoarthritis PainR01AG068997 · NIA · JOHNS HOPKINS UNIVERSITY · PI CAO, XU, GUAN, YUN · 2024 to 2024
$621k
NIAMS NIH HHS R01 AR063943NIA NIH HHS P01 AG066603NIA NIH HHS R01 AG068997NIA NIH HHS RF1 AG068997
6 · The paper itself

Abstract

Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFβ) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFβ activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFβ disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin-mediated TGFβ activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFβ activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFβ activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.

Indexed as

Stress, MechanicalAnimalsBone and BonesCartilage, ArticularCell LineChondrocytesCytoskeletonHomeostasisHumansIntegrin alphaVMiceMice, Inbred C57BLMice, TransgenicOsteoarthritisSignal TransductionTalinIntegrin alphaVTalinTransforming Growth Factor beta

Identifiers

PMID33731712
PMCPMC7969741
OpenAlexW3138613518

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.