Evidence map›Paper›PMID 36638270›Full record

ArticleAging cell2023

STAT3 promotes a youthful epigenetic state in articular chondrocytes.

Arijita Sarkar, Nancy Q Liu, Jenny Magallanes, Jade Tassey, Siyoung Lee, Ruzanna Shkhyan, Youngjoo Lee, Jinxiu Lu, Yuxin Ouyang, Hanhan Tang and 7 more

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

Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
9.4field-weighted citation impact, top 2% 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

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. 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

17 authors at 3 institutions in 1 country.

Arijita SarkarDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Nancy Q LiuDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Jenny MagallanesDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Jade TasseyDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Siyoung LeeDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Ruzanna ShkhyanDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Youngjoo LeeDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Jinxiu LuDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Yuxin OuyangDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Hanhan TangDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Fangzhou BianDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.
Litao TaoDepartment of Biomedical Sciences, Creighton University, Nebraska, Omaha, USA.
Neil SegilDepartment of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, California, USA.
Jason ErnstDepartment of Biological Chemistry, University of California, Los Angeles, California, USA.
Karen LyonsDepartment of Orthopaedic Surgery, University of California, Los Angeles, California, USA.
Steve HorvathDepartment of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, California, USA.ORCID 0000-0002-4110-3589
Denis EvseenkoDepartment of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California, USA.ORCID 0000-0002-8389-0015
University of Southern California · USUniversity of California, Los Angeles · USCreighton University · US

Funding

DOCTORAL AND POST-DOCTORAL TRAINING IN CRANIOFACIAL BIOLOGYT90DE021982 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PAINE, MICHAEL LANSDELL · 2011 to 2025
$6.2M
GP130/STAT3 signalling in articular cartilage development and regenerationR01AR071734 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EVSEENKO, DENIS, LYONS, KAREN M. · 2018 to 2022
$3.0M
Dissecting molecular mechanisms implicated in age- and osteoarthritis-related decline in anabolism in articular cartilageR01AG058624 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EVSEENKO, DENIS · 2019 to 2023
$1.7M
NIAMS NIH HHS R01 AR071734NIA NIH HHS R01 AG058624NIDCR NIH HHS T90 DE021982
6 · The paper itself

Abstract

Epigenetic mechanisms guiding articular cartilage regeneration and age-related disease such as osteoarthritis (OA) are poorly understood. STAT3 is a critical age-patterned transcription factor highly active in fetal and OA chondrocytes, but the context-specific role of STAT3 in regulating the epigenome of cartilage cells remain elusive. In this study, DNA methylation profiling was performed across human chondrocyte ontogeny to build an epigenetic clock and establish an association between CpG methylation and human chondrocyte age. Exposure of adult chondrocytes to a small molecule STAT3 agonist decreased DNA methylation, while genetic ablation of STAT3 in fetal chondrocytes induced global hypermethylation. CUT&RUN assay and subsequent transcriptional validation revealed DNA methyltransferase 3 beta (DNMT3B) as one of the putative STAT3 targets in chondrocyte development and OA. Functional assessment of human OA chondrocytes showed the acquisition of progenitor-like immature phenotype by a significant subset of cells. Finally, conditional deletion of Stat3 in cartilage cells increased DNMT3B expression in articular chondrocytes in the knee joint in vivo and resulted in a more prominent OA progression in a post-traumatic OA (PTOA) mouse model induced by destabilization of the medial meniscus (DMM). Taken together these data reveal a novel role for STAT3 in regulating DNA methylation in cartilage development and disease. Our findings also suggest that elevated levels of active STAT3 in OA chondrocytes may indicate an intrinsic attempt of the tissue to regenerate by promoting a progenitor-like phenotype. However, it is likely that chronic activation of this pathway, induced by IL-6 cytokines, is detrimental and leads to tissue degeneration.

Indexed as

Cartilage, ArticularOsteoarthritisAnimalsCells, CulturedChondrocytesDNA MethylationEpigenesis, GeneticHumansMiceSTAT3 Transcription FactorSTAT3 protein, humanSTAT3 Transcription Factorchondrocyte agingDNA methylationepigeneticsosteoarthritisregenerationSTAT3

Identifiers

PMID36638270
PMCPMC9924946
OpenAlexW4315927360

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.