ArticleDevelopmental biology2008
A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis.
Article in Developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 3 of them syntheses that pooled it.
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Who cites it
209 citing papers in PubMed, 3 syntheses or guidelines pooled it, 354 citations in OpenAlex.
- The role of synovial mesenchymal stem cell-derived exosomes in cartilage repair: a systematic review.Frontiers in pharmacology · 2025Pooled it
- Lubricin in experimental and naturally occurring osteoarthritis: a systematic review.Osteoarthritis and cartilage · 2020Pooled it
- Association between growth differentiation factor 5 rs143383 genetic polymorphism and the risk of knee osteoarthritis among Caucasian but not Asian: a meta-analysis.Arthritis research & therapy · 2020Pooled it
- Genetically Engineered Mouse Model in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Signaling and transcriptional networks governing late synovial joint development.Developmental biology · 2026Article
- Controlled release of CD200 inhibits inflammatory macrophages and chondrocyte catabolism.npj biomedical innovations · 2026Article
- Wnt/β-catenin signaling regulates fibrotic atrophy of intra-articular adipose tissue in post-traumatic osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- A pivotal Wnt antagonist role promoting digit joint specification by constraining Wnt activity.Nature communications · 2026Article
- Article
- Review
- The roles of TGF-β, Wnt, and MAPK signaling pathways in joint lineage specification in vitro and ex vivo.Stem cell reports · 2025Article
- Femur Shape Changes in Prg4-Deficient Mice: Morphological Insights Into Joint Well-Being.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Prx1NPJ Regenerative medicine · 2025Article
- Synovial joint cavitation during limb skeletogenesis entails Na/K-ATPase ion pump expression and osmoregulatory activity.Development (Cambridge, England) · 2025Article
- Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Creb5 controls its own expression and directly induces the joint interzone regulatory program.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation.Biomedicines · 2025Article
- PTPN11 in cartilage development, adult homeostasis, and diseases.Bone research · 2025Review
- PDGFRα signaling regulates cartilage and fibrous tissue differentiation during synovial joint development.Nature communications · 2025Article
- Stem and progenitor cells in the synovial joint as targets for regenerative therapy.Nature reviews. Rheumatology · 2025Review
149 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The origin, roles and fate of progenitor cells forming synovial joints during limb skeletogenesis remain largely unclear. Here we produced prenatal and postnatal genetic cell fate-maps by mating ROSA-LacZ-reporter mice with mice expressing Cre-recombinase at prospective joint sites under the control of Gdf5 regulatory sequences (Gdf5-Cre). Reporter-expressing cells initially constituted the interzone, a compact mesenchymal structure representing the first overt sign of joint formation, and displayed a gradient-like distribution along the ventral-to-dorsal axis. The cells expressed genes such as Wnt9a, Erg and collagen IIA, remained predominant in the joint-forming sites over time, gave rise to articular cartilage, synovial lining and other joint tissues, but contributed little if any to underlying growth plate cartilage and shaft. To study their developmental properties more directly, we isolated the joint-forming cells from prospective autopod joint sites using a novel microsurgical procedure and tested them in vitro. The cells displayed a propensity to undergo chondrogenesis that was enhanced by treatment with exogenous rGdf5 but blocked by Wnt9a over-expression. To test roles for such Wnt-mediated anti-chondrogenic capacity in vivo, we created conditional mutants deficient in Wnt/beta-catenin signaling using Col2-Cre or Gdf5-Cre. Synovial joints did form in both mutants; however, the joints displayed a defective flat cell layer normally abutting the synovial cavity and expressed markedly reduced levels of lubricin. In sum, our data indicate that cells present at prospective joint sites and expressing Gdf5 constitute a distinct cohort of progenitor cells responsible for limb joint formation. The cells appear to be patterned along specific limb symmetry axes and rely on local signaling tools to make distinct contributions to joint formation.
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Registered trials
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.