Evidence map›Paper›PMID 24155967›Full record

ArticlePloS one2013

BMP12 induces tenogenic differentiation of adipose-derived stromal cells.

Hua Shen, Richard H Gelberman, Matthew J Silva, Shelly E Sakiyama-Elbert, Stavros Thomopoulos

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

62 citing papers in PubMed, 117 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Biomimetic Scaffolds for Tendon Tissue Regeneration.Biomimetics (Basel, Switzerland) · 2023
    Review
  11. Article
  12. Growth factors in the treatment of Achilles tendon injury.Frontiers in bioengineering and biotechnology · 2023
    Review
  13. Age-related cellular and microstructural changes in the rotator cuff enthesis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

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

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

5 authors at 1 institution in 1 country.

Hua ShenDepartment of Orthopaedic Surgery, Washington University, St. Louis, Missouri, United States of America.
Richard H Gelberman
Matthew J Silva
Shelly E Sakiyama-Elbert
Stavros Thomopoulos
Washington University in St. Louis · US

Funding

Enhanced Tendon Healing Through Growth Factor and Cell TherapiesR01AR062947 · NIAMS · WASHINGTON UNIVERSITY · PI GELBERMAN, RICHARD H, THOMOPOULOS, STAVROS · 2012 to 2022
$5.5M
NIAMS NIH HHS AR062947NIAMS NIH HHS R01 AR062947
6 · The paper itself

Abstract

Adipose-derived stromal cells (ASCs) are pluripotent cells that have the capacity to differentiate into tendon fibroblasts (TFs). They are abundant in adults, easy to access, and are therefore an ideal cell source for tendon tissue engineering. Despite this potential, the molecular cues necessary for tenogenic differentiation of ASCs are unknown. Unlike other bone morphogenetic proteins (BMPs), BMP12, BMP13, and BMP14 have been reported to be less osteo-chondrogenic and to induce tendon rather than bone formation in vivo. This study investigated the effects of BMP12 and BMP14 on ASC differentiation in vitro. In canine ASCs, BMP12 effectively increased the expression of the tendon markers scleraxis and tenomodulin at both mRNA and protein levels. Consistent with these results, BMP12 induced scleraxis promoter driven-GFP and tenomodulin protein expression in mouse ASCs. Although BMP12 also enhanced the expression of the cartilage matrix gene aggrecan in ASCs, the resulting levels remained considerably lower than those detected in tendon fibroblasts. In addition, BMP12 reduced expression of the bone marker osteocalcin, but not the osteogenic transcription factor runx-2. BMP14 exhibited similar, but marginally less potent and selective effects, compared to BMP12. BMPs are known to signal through the canonical Smad pathway and the non-canonical mitogen-activated protein kinase (MAPK) pathway. BMP12 triggered robust phosphorylation of Smad1/5/8 but not Smad2/3 or p38 MAPK in ASCs. The effect was likely conveyed by type I receptors ALK2/3/6, as phosphorylation of Smad1/5/8 was blocked by the ALK2/3/6 inhibitor LDN-193189 but not by the ALK4/5/7 inhibitor SB-505124. Moreover, ALK6 was found to be the most abundant type I receptor in ASCs, with mRNA expression 100 to 10,000 times that of any other type I receptor. Collectively, results support the conclusion that BMP12 induces tenogenic differentiation of ASCs via the Smad1/5/8 pathway.

Indexed as

Activin Receptors, Type IIAdipose TissueAnimalsBone Morphogenetic ProteinsCell DifferentiationColony-Forming Units AssayDogsGene Expression RegulationGreen Fluorescent ProteinsGrowth Differentiation FactorsMembrane ProteinsMicePromoter Regions, GeneticSignal TransductionSmad ProteinsStromal CellsActivin Receptors, Type IIBone Morphogenetic ProteinsGDF7 protein, humanGreen Fluorescent ProteinsGrowth Differentiation FactorsMembrane ProteinsSmad ProteinsTranscription Factors

Identifiers

PMID24155967
PMCPMC3796462
OpenAlexW1984071676

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.