Evidence map›Paper›PMID 25047145›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2014

Use of cartilage derived from murine induced pluripotent stem cells for osteoarthritis drug screening.

Vincent P Willard, Brian O Diekman, Johannah Sanchez-Adams, Nicolas Christoforou, Kam W Leong, Farshid Guilak

Abstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.3field-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

31 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Chondrogenic Differentiation of Human-Induced Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Cell Interplay in Osteoarthritis.Frontiers in cell and developmental biology · 2021
    Review
  16. The miRNA-mRNA interactome of murine induced pluripotent stem cell-derived chondrocytes in response to inflammatory cytokines.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  17. Review
  18. Inhibition of MMPs and ADAM/ADAMTS.Biochemical pharmacology · 2019
    Review
  19. Designer Stem Cells: Genome Engineering and the Next Generation of Cell-Based Therapies.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019
    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

6 authors at 2 institutions in 2 countries.

Vincent P WillardDuke University Medical Center, Durham, North Carolina.
Brian O Diekman
Johannah Sanchez-Adams
Nicolas Christoforou
Kam W Leong
Farshid Guilak
Duke Medical Center · USDuke University · US

Funding

Thermally-Triggered Intra-articular Drug Delivery for OAP01AR050245 · NIAMS · DUKE UNIVERSITY · PI GUILAK, FARSHID · 2003 to 2012
$11.5M
VISCOELASTIC PROPERTIES OF NORMAL AND OA CHONDRONSR01AG015768 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 1998 to 2022
$7.7M
TRAINING PROGRAM IN INFLAMMATORY AND IMMUNOLOGICALT32AI007217 · NIAID · DUKE UNIVERSITY · PI PISETSKY, DAVID STEPHEN · 1985 to 2015
$3.3M
OBESITY, BIOMECHANICS, AND INFLAMMATION IN OSTEOARTHRITISR01AG046927 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 2013 to 2023
$3.2M
Mechanical and Osmotic Signaling in ChondrocytesR01AR048182 · NIAMS · DUKE UNIVERSITY · PI GUILAK, FARSHID · 2003 to 2013
$3.0M
Intrinsic Repair of the Knee MeniscusR01AR048852 · NIAMS · DUKE UNIVERSITY · PI GUILAK, FARSHID · 2007 to 2011
$1.4M
Genome Editing of Stem Cells for Analysis of Osteoarthritis Causal VariantsR21AR065956 · NIAMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A., GUILAK, FARSHID · 2014 to 2015
$382k
NIAID NIH HHS T32 AI007217NIAID NIH HHS T32-AI-007217NIAMS NIH HHS AR-48182NIAMS NIH HHS AR-48852NIAMS NIH HHS AR-50245NIAMS NIH HHS P01 AR050245NIAMS NIH HHS R01 AR048182NIAMS NIH HHS R01 AR048852NIAMS NIH HHS R21 AR065956NIA NIH HHS AG-15768NIA NIH HHS AG-46927NIA NIH HHS R01 AG015768NIA NIH HHS R01 AG046927
6 · The paper itself

Abstract

objectiveThe discovery of novel disease-modifying drugs for osteoarthritis (OA) is limited by the lack of adequate genetically defined cartilage tissues for application in high-throughput screening systems. We addressed this need by synthesizing cartilage from induced pluripotent stem cells (iPSCs) to establish and validate an in vitro model of OA.

methodsNative or iPSC-derived mouse cartilage samples were treated with the cytokine interleukin-1α (IL-1α) for 3 days to model the inflammatory environment of OA. The biochemical content, mechanical properties, and gene expression of the resulting tissues were assayed. In addition, the inflammatory and catabolic environment of the media was assessed. To establish high-throughput capability, we used a 96-well plate format and conducted a screen of previously identified candidate OA drugs. Glycosaminoglycan (GAG) release into the medium was used as the primary output for screening.

resultsTreatment of iPSC-derived or native cartilage with IL-1α induced characteristic features of OA in a rapid and dose-dependent manner. In addition to the loss of GAGs and tissue mechanical properties, IL-1α treatment induced the expression of matrix metalloproteinases and increased the production of the inflammatory mediators nitric oxide and prostaglandin E2 . In the high-throughput screen validation, all candidate OA therapeutic agents provided some benefit, but only the NF-κB inhibitor SC514 effectively reduced cartilage loss in response to IL-1α.

conclusionThis work demonstrates the utility of iPSCs for studying cartilage pathology and provides a platform for identifying novel, patient-specific therapeutic agents that prevent cartilage degradation and modify the course of OA development.

Indexed as

Cell DifferentiationAnimalsAntirheumatic AgentsCartilageCells, CulturedDisease Models, AnimalDrug Evaluation, PreclinicalGene Expression RegulationGlycosaminoglycansHigh-Throughput Screening AssaysInterleukin-1alphaIn Vitro TechniquesMiceMice, Inbred C57BLOsteoarthritisPluripotent Stem CellsAntirheumatic AgentsGlycosaminoglycansInterleukin-1alpha

Identifiers

PMID25047145
PMCPMC4308724
OpenAlexW1807713007

What OpenQuestion holds

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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.