ArticleScience signaling2023
Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis.
Article in Science signaling, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Osteoarthritic synovial fibroblasts drive inflammatory responses and impair chondrocyte function in response to a fibronectin matrikine.Osteoarthritis and cartilage · 2026Article
- CSPG4Osteoarthritis and cartilage open · 2026Article
- Targeting mechanotransduction components as therapeutic strategies in osteoarthritis.Molecular biology reports · 2026Review
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Investigating the mechanisms by which bisphenol A affects osteoarthritis through a novel network toxicology framework and experimental validation.BMC pharmacology & toxicology · 2026Article
- Microenvironmental response-based treatment of osteoarthritis is a highly effective and durable program: a review.Journal of orthopaedic surgery and research · 2025Review
- Observational
- The Reciprocal Relationship Between Cell Adhesion Molecules and Reactive Oxygen Species.Cells · 2025Review
- Proteomic analysis of hydrogen peroxide-treated human chondrocytes shows endoplasmic reticulum stress, cytoskeleton remodeling, and altered secretome composition.Cell communication and signaling : CCS · 2025Article
- Endosomal HAntioxidants (Basel, Switzerland) · 2025Article
- The role and regulation of integrins in cell migration and invasion.Nature reviews. Molecular cell biology · 2025Review
- Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.Cell genomics · 2025Article
- Role and mechanism of Integrin α5β1 in bone formation and disease.Frontiers in cell and developmental biology · 2025Review
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.bioRxiv : the preprint server for biology · 2024Article
- Integrin signalling in joint development, homeostasis and osteoarthritis.Nature reviews. Rheumatology · 2024Review
- Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis.Frontiers in immunology · 2024Article
- A novel small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery.PloS one · 2024Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
Mechanical cues sensed by integrins induce cells to produce proteases to remodel the extracellular matrix. Excessive protease production occurs in many degenerative diseases, including osteoarthritis, in which articular cartilage degradation is associated with the genesis of matrix protein fragments that can activate integrins. We investigated the mechanisms by which integrin signals may promote protease production in response to matrix changes in osteoarthritis. Using a fragment of the matrix protein fibronectin (FN) to activate the α5β1 integrin in primary human chondrocytes, we found that endocytosis of the integrin and FN fragment complex drove the production of the matrix metalloproteinase MMP-13. Activation of α5β1 by the FN fragment, but not by intact FN, was accompanied by reactive oxygen species (ROS) production initially at the cell surface, then in early endosomes. These ROS-producing endosomes (called redoxosomes) contained the integrin-FN fragment complex, the ROS-producing enzyme NADPH oxidase 2 (NOX2), and SRC, a redox-regulated kinase that promotes MMP-13 production. In contrast, intact FN was endocytosed and trafficked to recycling endosomes without inducing ROS production. Articular cartilage from patients with osteoarthritis showed increased amounts of SRC and the NOX2 complex component p67
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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.