Evidence map›Paper›PMID 22768305›Full record

ArticlePloS one2012

Interplay of Nkx3.2, Sox9 and Pax3 regulates chondrogenic differentiation of muscle progenitor cells.

Dana M Cairns, Renjing Liu, Manpreet Sen, James P Canner, Aaron Schindeler, David G Little, Li Zeng

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Harnessing Endogenous Cellular Mechanisms for Bone Repair.Frontiers in bioengineering and biotechnology · 2017
    Review
  14. Article
  15. Article
  16. Muscle-bone interactions during fracture healing.Journal of musculoskeletal & neuronal interactions · 2015
    Review
  17. Article
  18. The role of Nkx3.2 in chondrogenesis.Frontiers in biology · 2014
    Article
  19. Molecular mechanisms of heterotopic ossification.The Journal of hand surgery · 2014
    Review
  20. Article
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

7 authors at 4 institutions in 2 countries.

Dana M CairnsProgram in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.
Renjing Liu
Manpreet Sen
James P Canner
Aaron Schindeler
David G Little
Li Zeng
Tufts University · USChildren's Hospital at Westmead · AUTufts Medical Center · USUniversity of Sydney · AU

Funding

UNTHSC Summer Multicultural Advanced Research Training Program "SMART"R25HL007786 · NHLBI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI JONES, HARLAN PIERRE · 2008 to 2023
$2.1M
Muscle Cell-Enhanced Cartilage Tissue EngineeringR01AR059106 · NIAMS · TUFTS UNIVERSITY BOSTON · PI ZENG, LI · 2010 to 2014
$1.8M
Nkx3.2 nuclear localization and cartlidge formationR03AR054611 · NIAMS · TUFTS UNIVERSITY BOSTON · PI ZENG, LI · 2007 to 2009
$242k
Medical Research Council 457245NHLBI NIH HHS 5R25HL007786NHLBI NIH HHS R25 HL007786NIAMS NIH HHS R01 AR059106NIAMS NIH HHS R01AR059106NIAMS NIH HHS R03 AR054611
6 · The paper itself

Abstract

Muscle satellite cells make up a stem cell population that is capable of differentiating into myocytes and contributing to muscle regeneration upon injury. In this work we investigate the mechanism by which these muscle progenitor cells adopt an alternative cell fate, the cartilage fate. We show that chick muscle satellite cells that normally would undergo myogenesis can be converted to express cartilage matrix proteins in vitro when cultured in chondrogenic medium containing TGFß3 or BMP2. In the meantime, the myogenic program is repressed, suggesting that muscle satellite cells have undergone chondrogenic differentiation. Furthermore, ectopic expression of the myogenic factor Pax3 prevents chondrogenesis in these cells, while chondrogenic factors Nkx3.2 and Sox9 act downstream of TGFß or BMP2 to promote this cell fate transition. We found that Nkx3.2 and Sox9 repress the activity of the Pax3 promoter and that Nkx3.2 acts as a transcriptional repressor in this process. Importantly, a reverse function mutant of Nkx3.2 blocks the ability of Sox9 to both inhibit myogenesis and induce chondrogenesis, suggesting that Nkx3.2 is required for Sox9 to promote chondrogenic differentiation in satellite cells. Finally, we found that in an in vivo mouse model of fracture healing where muscle progenitor cells were lineage-traced, Nkx3.2 and Sox9 are significantly upregulated while Pax3 is significantly downregulated in the muscle progenitor cells that give rise to chondrocytes during fracture repair. Thus our in vitro and in vivo analyses suggest that the balance of Pax3, Nkx3.2 and Sox9 may act as a molecular switch during the chondrogenic differentiation of muscle progenitor cells, which may be important for fracture healing.

Indexed as

Cell DifferentiationChondrogenesisFracture HealingAnimalsBone Morphogenetic Protein 2Cells, CulturedChick EmbryoChickensFractures, BoneHomeodomain ProteinsMiceMuscle DevelopmentMuscle ProteinsPaired Box Transcription FactorsPAX3 Transcription FactorSatellite Cells, Skeletal MuscleBmp2 protein, mouseBone Morphogenetic Protein 2Homeodomain ProteinsMuscle ProteinsNkx3-2 protein, mousePaired Box Transcription FactorsPax3 protein, mousePAX3 Transcription FactorSox9 protein, mouseSOX9 Transcription FactorTranscription FactorsTransforming Growth Factor beta

Identifiers

PMID22768305
PMCPMC3388093
OpenAlexW2081501298

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.