ArticleThe Journal of biological chemistry2013
Epidermal growth factor receptor (EGFR) signaling regulates epiphyseal cartilage development through β-catenin-dependent and -independent pathways.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
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- Data-driven selection of analysis decisions in single-cell RNA-seq trajectory inference.Briefings in bioinformatics · 2024Article
- Data-driven selection of analysis decisions in single-cell RNA-seq trajectory inference.bioRxiv : the preprint server for biology · 2023Article
- EGFR Signaling Is Required for Maintaining Adult Cartilage Homeostasis and Attenuating Osteoarthritis Progression.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Unbiased comparison and modularization identify time-related transcriptomic reprogramming in exercised rat cartilage: Integrated data mining and experimental validation.Frontiers in physiology · 2022Article
- Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights.Open life sciences · 2022Review
- Identification and validation of hub genes of synovial tissue for patients with osteoarthritis and rheumatoid arthritis.Hereditas · 2021Article
- Targeting cartilage EGFR pathway for osteoarthritis treatment.Science translational medicine · 2021Article
- Article
- Overexpression of MIG-6 in the cartilage induces an osteoarthritis-like phenotype in mice.Arthritis research & therapy · 2020Article
- Opportunities and challenges of co-targeting epidermal growth factor receptor and autophagy signaling in non-small cell lung cancer.Oncology letters · 2019Review
- Periarticular Mesenchymal Progenitors Initiate and Contribute to Secondary Ossification Center Formation During Mouse Long Bone Development.Stem cells (Dayton, Ohio) · 2019Article
- The Influence of TGF-β3, EGF, and BGN on SOX9 and RUNX2 Expression in Human Chondrogenic Progenitor Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Article
- EGFR Signaling: Friend or Foe for Cartilage?JBMR plus · 2019Review
- EGF-induced nuclear localization of SHCBP1 activates β-catenin signaling and promotes cancer progression.Oncogene · 2019Article
- Epidermal growth factor can signal via β-catenin to control proliferation of mesenchymal stem cells independently of canonical Wnt signalling.Cellular signalling · 2019Article
- Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment.EBioMedicine · 2018Article
- Loading-Induced Reduction in Sclerostin as a Mechanism of Subchondral Bone Plate Sclerosis in Mouse Knee Joints During Late-Stage Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The epidermal growth factor receptor (EGFR) is an essential player in the development of multiple organs during embryonic and postnatal stages. To understand its role in epiphyseal cartilage development, we generated transgenic mice with conditionally inactivated EGFR in chondrocytes. Postnatally, these mice exhibited a normal initiation of cartilage canals at the perichondrium, but the excavation of these canals into the cartilage was strongly suppressed, resulting in a delay in the formation of the secondary ossification center (SOC). This delay was accompanied by normal chondrocyte hypertrophy but decreased mineralization and apoptosis of hypertrophic chondrocytes and reduced osteoclast number at the border of marrow space. Immunohistochemical analyses demonstrated that inactivation of chondrocyte-specific EGFR signaling reduced the amounts of matrix metalloproteinases (MMP9, -13, and -14) and RANKL (receptor activator of NF-κB ligand) in the hypertrophic chondrocytes close to the marrow space and decreased the cartilage matrix degradation in the SOC. Analyses of EGFR downstream signaling pathways in primary epiphyseal chondrocytes revealed that up-regulation of MMP9 and RANKL by EGFR signaling was partially mediated by the canonical Wnt/β-catenin pathway, whereas EGFR-enhanced MMP13 expression was not. Further biochemical studies suggested that EGFR signaling stimulates the phosphorylation of LRP6, increases active β-catenin level, and induces its nuclear translocation. In line with these in vitro studies, deficiency in chondrocyte-specific EGFR activity reduced β-catenin amount in hypertrophic chondrocytes in vivo. In conclusion, our work demonstrates that chondrocyte-specific EGFR signaling is an important regulator of cartilage matrix degradation during SOC formation and epiphyseal cartilage development and that its actions are partially mediated by activating the β-catenin pathway.
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