Evidence map›Paper›PMID 41135529›Full record

ArticleStem cell reports2025

The roles of TGF-β, Wnt, and MAPK signaling pathways in joint lineage specification in vitro and ex vivo.

Suyash Raj, Thomas Cutia, Stefano Menghini, Mireia Alemany-Ribes, Junming Cai, Mariel Young, Sarah K Jachim, Terence D Capellini, April M Craft

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Suyash RajDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA.
Thomas CutiaDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA.
Stefano MenghiniDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA.
Mireia Alemany-RibesDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA; Department of Orthopedic Surgery, Harvard Medical School, Boston, MA, USA.
Junming CaiDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA.
Mariel YoungHuman Evolutionary Biology, Harvard University, Cambridge, MA, USA.
Sarah K JachimDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA.
Terence D CapelliniHuman Evolutionary Biology, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
April M CraftDepartment of Orthopedic Surgery, Boston Children's Hospital, Boston, MA, USA; Department of Orthopedic Surgery, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA. Electronic address: april.craft@childrens.harvard.edu.

Funding

Translational Imaging and Phenotyping CoreP30AR075042 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI Marie Demay · 2019 to 2026
$7.4M
Uncovering the Genetic Mechanisms Behind Joint-Specific OsteoarthritisR01AR070139 · NIAMS · HARVARD UNIVERSITY · PI CAPELLINI, TERENCE D · 2018 to 2022
$3.3M
Defining the Human Articular Chondrocyte LineageR01AR073821 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI CRAFT, APRIL MARIE · 2019 to 2023
$2.7M
NIAMS NIH HHS P30 AR075042NIAMS NIH HHS R01 AR070139NIAMS NIH HHS R01 AR073821
6 · The paper itself

Abstract

The initiation of synovial joint development and subsequent differentiation of progenitor cells toward anatomically and functionally distinct joint tissues are not well understood, despite being highly relevant to joint health and disease. We generated a dual reporter mouse embryonic stem cell (mESC) line to quantify cells expressing growth differentiation factor five (Gdf5), an early marker of joint formation, and Prg4, a lubricating proteoglycan found in joint tissues. Transforming growth factor β (TGF-β) signaling was necessary and sufficient for the induction of Gdf5-RFP and Prg4-GFP. Inhibition of either Wnt or MAPK signaling significantly increased the induction of Gdf5-RFP, while activation of either pathway prohibited this induction. Single cell transcriptomics demonstrated the chondrogenic identity of Gdf5+ cells in in vitro cultures and in mouse embryonic limb buds. We validated the roles of these signaling pathways in joint-specific ex vivo limb bud cultures. Thus, this in vitro model enhances our understanding of joint development and offers new insights into potential therapeutic approaches for joint disorders.

Indexed as

Cell LineageJointsMAP Kinase Signaling SystemTransforming Growth Factor betaWnt Signaling PathwayAnimalsCell DifferentiationCell LineChondrogenesisGrowth Differentiation Factor 5Limb BudsMiceMouse Embryonic Stem CellsProteoglycansSignal TransductionGrowth Differentiation Factor 5ProteoglycansTransforming Growth Factor betaESCsFGFGdf5interzonejointlimb budPrg4tendonTGF-betaWnt

Identifiers

PMID41135529
PMCPMC12790734

What Socratic 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 Socratic graph.