ArticleProceedings of the National Academy of Sciences of the United States of America2016
EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 107 citations in OpenAlex.
- Acute TGFα drives OA-associated transcriptional and metabolic remodelling in primary chondrocytes.Osteoarthritis and cartilage open · 2026Article
- Variation in Intrinsic Aerobic Capacity Reveals Distinct Differences in the Maintenance of Rat Knee Joint Integrity.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- The role of the HB-EGF-regulated EGFR-mitophagy axis in maintaining cartilage homeostasis and osteoarthritis.Journal of molecular histology · 2026Article
- Transcriptome analysis in osteoarthritis primary tissues identifies high-confidence effector genes.Nature communications · 2026Article
- Investigating the mechanisms by which bisphenol A affects osteoarthritis through a novel network toxicology framework and experimental validation.BMC pharmacology & toxicology · 2026Article
- Molecular characterization of superficial zone chondrocytes under pro-inflammatory and biomechanical stress conditions.PloS one · 2026Article
- MAPK Pathway Activation Patterns in the Synovium Reveal ERK1/2 and EGFR as Key Players in Osteoarthritis.Biomedicines · 2025Article
- Stem cell-derived small extracellular vesicles containing miR-27b-3p attenuated osteoarthritis through inhibition of leukaemia inhibitory factor.Fundamental research · 2025Article
- Hand Osteoarthritis: Molecular Mechanisms, Randomized Controlled Trials, and the Future of Targeted Treatment.International journal of molecular sciences · 2025Review
- Review
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Integrated multi-omics and machine learning reveals immune-metabolic signatures in osteoarthritis: from bulk RNA-seq to single-cell resolution.Frontiers in immunology · 2025Article
- Nanomaterials in the diagnosis and therapy of osteoarthritis: current research advances and future clinical prospects.Frontiers in bioengineering and biotechnology · 2025Review
- Hesperetin Attenuates T-2 Toxin-Induced Chondrocyte Injury by Inhibiting the p38 MAPK Signaling Pathway.Nutrients · 2024Article
- HSPB1 as an RNA-binding protein mediates the pathological process of osteoarthritis.Journal of orthopaedic surgery and research · 2024Article
- Calycosin ameliorates osteoarthritis by regulating the imbalance between chondrocyte synthesis and catabolism.BMC complementary medicine and therapies · 2024Article
- Mechanical Signal Transduction: A Key Role of Fluid Shear Forces in the Development of Osteoarthritis.Journal of inflammation research · 2024Review
- Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Effects and action mechanisms of individual cytokines contained in PRP on osteoarthritis.Journal of orthopaedic surgery and research · 2023Review
- Identification of EGFR as an essential regulator in chondrocytes ferroptosis of osteoarthritis using bioinformatics,Heliyon · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation.
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