ArticleCell death & disease2021
MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- FGFR1/KLB-MFG-E8 Maintains Microvascular Integrity and Adaptive Cardiac Remodeling.Circulation research · 2026Article
- Ultrasound-Activatable Piezoelectric Hydrogel Reprograms Mitochondrial Epigenetics for Osteoarthritis Therapy via the mTOR/GATD3A Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The signaling and regulatory functions of dying cells and cell corpses.Communications biology · 2026Review
- Immunosenescence and Bone Homeostasis: From Mechanisms of Homeostasis Disruption to Therapeutic Opportunities in Age-Related Skeletal Disorders.International journal of molecular sciences · 2026Review
- Unraveling key molecules mediating the mechanisms of YAP deletion or inhibition in liver fibrosis regression through a multi-omics approach.Histology and histopathology · 2026Article
- CAP-CD56Bioactive materials · 2026Article
- Chondrocyte Senescence in Osteoarthritis: Potential Targets and Pharmacological Interventions.Cartilage · 2026Article
- Paradigm shift in macrophage polarization in osteoarthritis: from M1/M2 imbalance to macrophage state reprogramming in the ageing immune microenvironment.Frontiers in immunology · 2026Review
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis.International journal of molecular sciences · 2025Article
- Macrophages: pivotal orchestrators and emerging therapeutic targets in osteoarthritis pathogenesis.Journal of translational medicine · 2025Review
- Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy.Molecular cancer · 2025Review
- Extracellular vesicle bioactivity and potential for clinical development are determined by mesenchymal stromal cell clonal subtype.Stem cell research & therapy · 2025Article
- Emerging Therapy in Osteoarthritis: Mesenchymal Stem Cells, Secretomes, and Using Hydrogels to Enhance Efficacy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- The Age-dependent Influence of the Infrapatellar Fat Pad on Chondrocyte Extracellular Matrix Production.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Role of lysine lactylation in neoplastic and inflammatory pulmonary diseases (Review).International journal of molecular medicine · 2025Review
- An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration.Nature communications · 2025Article
- The miR-6779/XIAP axis alleviates IL-1β-induced chondrocyte senescence and extracellular matrix loss in osteoarthritis.Animal models and experimental medicine · 2025Article
- Macrophage Polarization in the Osteoarthritis Pathogenesis and Treatment.Orthopaedic surgery · 2025Review
- SPACA6-hosted miR-99b~125a~let-7e cluster shapes melanoma resistance by modulating mTOR-mediated immunosuppression.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Milk fat globule-epidermal growth factor (EGF) factor 8 (MFG-E8), as a necessary bridging molecule between apoptotic cells and phagocytic cells, has been widely studied in various organs and diseases, while the effect of MFG-E8 in osteoarthritis (OA) remains unclear. Here, we identified MFG-E8 as a key factor mediating chondrocyte senescence and macrophage polarization and revealed its role in the pathology of OA. We found that MFG-E8 expression was downregulated both locally and systemically as OA advanced in patients with OA and in mice after destabilization of the medial meniscus surgery (DMM) to induce OA. MFG-E8 loss caused striking progressive articular cartilage damage, synovial hyperplasia, and massive osteophyte formation in OA mice, which was relieved by intra-articular administration of recombinant mouse MFG-E8 (rmMFG-E8). Moreover, MFG-E8 restored chondrocyte homeostasis, deferred chondrocyte senescence and reprogrammed macrophages to the M2 subtype to alleviate OA. Further studies showed that MFG-E8 was inhibited by miR-99b-5p, expression of which was significantly upregulated in OA cartilage, leading to exacerbation of experimental OA partially through activation of NF-κB signaling in chondrocytes. Our findings established an essential role of MFG-E8 in chondrocyte senescence and macrophage reprogramming during OA, and identified intra-articular injection of MFG-E8 as a potential therapeutic target for OA prevention and treatment.
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