ArticleJCI insight2019
Dysregulated integrin αVβ3 and CD47 signaling promotes joint inflammation, cartilage breakdown, and progression of osteoarthritis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 72 citations in OpenAlex.
- Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.Journal of biomedical science · 2026Review
- Targeting mechanotransduction components as therapeutic strategies in osteoarthritis.Molecular biology reports · 2026Review
- Viral glycoprotein-mimicking peptide-functionalized micelles promote drug delivery to diseased chondrocytes for osteoarthritis alleviation.Nature nanotechnology · 2026Article
- Applications of fullerenes in the treatment of osteoarthritis.Nanomedicine (London, England) · 2026Review
- Cancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CD47/SIRPα pathways: Functional diversity and molecular mechanisms.World journal of biological chemistry · 2025Review
- Breaking Down Osteoarthritis: Exploring Inflammatory and Mechanical Signaling Pathways.Life (Basel, Switzerland) · 2025Review
- Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice.Cell death discovery · 2025Article
- Chondrocyte lysates activate NLRP3 inflammasome-induced pyroptosis in synovial fibroblasts to exacerbate knee synovitis by downregulating caveolin-1.Arthritis research & therapy · 2025Article
- TNF induces catabolism in human cartilaginous endplate cells in 3D agarose culture under dynamic compression.Scientific reports · 2025Article
- CD47 is required for mesenchymal progenitor proliferation and fracture repair.Bone research · 2025Article
- Structure, Properties, and Biomedical Activity of Natural Sweeteners Steviosides: An Update.Food science & nutrition · 2025Review
- Role and mechanism of Integrin α5β1 in bone formation and disease.Frontiers in cell and developmental biology · 2025Review
- Passive hydrotherapy preserves cartilage and muscle integrity in a murine osteoarthritis model: potential role of integrin αV/TGF-β mechanotransduction.Frontiers in physiology · 2025Article
- Serum miRNA-186-3P and miRNA-382-3P constitute a novel Diagnostic miRNA signature for palindromic rheumatism.Frontiers in immunology · 2025Article
- The potential key genes within focal adhesion that regulate mesenchymal stem cells osteogenesis or adipogenesis in microgravity related disuse osteoporosis: an integrated analysis.Frontiers in endocrinology · 2025Article
- Silk films with distinct surface topography modulate plasma membrane curvature to polarize macrophages.Materials today. Bio · 2024Article
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Cell-recruited microspheres for OA treatment by dual-modulating inflammatory and chondrocyte metabolism.Materials today. Bio · 2024Article
- Integrin signalling in joint development, homeostasis and osteoarthritis.Nature reviews. Rheumatology · 2024Review
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 3 countries.
Funding
Abstract
Osteoarthritis (OA) is the leading cause of joint failure, yet the underlying mechanisms remain elusive, and no approved therapies that slow progression exist. Dysregulated integrin function was previously implicated in OA pathogenesis. However, the roles of integrin αVβ3 and the integrin-associated receptor CD47 in OA remain largely unknown. Here, transcriptomic and proteomic analyses of human and murine osteoarthritic tissues revealed dysregulated expression of αVβ3, CD47, and their ligands. Using genetically deficient mice and pharmacologic inhibitors, we showed that αVβ3, CD47, and the downstream signaling molecules Fyn and FAK are crucial to OA pathogenesis. MicroPET/CT imaging of a mouse model showed elevated ligand-binding capacities of integrin αVβ3 and CD47 in osteoarthritic joints. Further, our in vitro studies demonstrated that chondrocyte breakdown products, derived from articular cartilage of individuals with OA, induced αVβ3/CD47-dependent expression of inflammatory and degradative mediators, and revealed the downstream signaling network. Our findings identify a central role for dysregulated αVβ3 and CD47 signaling in OA pathogenesis and suggest that activation of αVβ3 and CD47 signaling in many articular cell types contributes to inflammation and joint destruction in OA. Thus, the data presented here provide a rationale for targeting αVβ3, CD47, and their signaling pathways as a disease-modifying therapy.
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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.