ArticleNature communications2025
PDGFRα signaling regulates cartilage and fibrous tissue differentiation during synovial joint development.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Signaling and transcriptional networks governing late synovial joint development.Developmental biology · 2026Article
- Motion as Medicine: Physical Activity, Joint Sensitivity, and Pain Management-A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- PDGF signaling regulates the adipocyte-to-fibroblast transition in wound healing.Cell reports · 2026Article
- Spatiotemporal Regulation and Lineage Specification in Embryonic Endochondral Ossification.International journal of molecular sciences · 2026Review
- A bio-adaptive physical hydrogel enables dynamic tissue engineering for tracheal reconstruction.Nature communications · 2025Article
- Gli1-expressing stromal cells are highly reparative precursors of long-lived chondroprogenitors in the fetal murine limb.Nature communications · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Synovial joints develop from mesenchymal structures called interzones, with progenitor cells differentiating into specialized cartilaginous and fibrous tissues of the joint. Platelet-derived growth factor receptor-α (PDGFRα) is a tyrosine kinase expressed by cells of the limb bud, but its role in limb development is unknown. To investigate PDGFRα function, we generated mice expressing mutant PDGFRα with a point mutation (D842V) that increases receptor signaling. Mutant hindlimbs are immobile with knee joints fused by cartilage and lacking ligaments and menisci. The interzone marker Gdf5 is initially expressed at E12.5 but is downregulated thereafter, suggesting a defect in interzone maintenance. Omics analysis of the joint tissues identifies ectopic cartilage matrix expressing genes for cartilage and fibrotic tissue. Thus, elevated PDGFRα signaling corrupts joint development by downregulating Gdf5 and redirecting interzone progenitors into a fibrocartilage fate. This suggests that tight regulation of tyrosine kinase activity is necessary for the development of the mouse knee joint.
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Registered trials
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