| Gene name: | MFGE8 |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | Chondrocyte |
| Gene ID: | 4240 |
| Category: | protein coding |
| Phenotype: | Osteoarthritis |
| Experimental category: | L |
| PMID: | 34031369 |
| Experiment: | SA-β-gal activity assay//Immunofluorescence//Western blot |
| Description: | β-galactosidase staining revealed that rmMFG-E8 markedly rescued the senescence phenotype induced by IL-1β in primary murine chondrocytes. Senescence-related hallmarks P16, P21 and P53 were significantly downregulated after ectopic application of MFG-E8 in IL-1β-pretreated primary chondrocytes, while MFG-E8 loss strongly promoted the expression of these senescence factors. Intraarticular injection of MFG-E8 neutralizing antibody obviously upregulated senescence markers, which were suppressed by rmMFG-E8, indicating the protective effect of MFG-E8 against chondrocyte senescence. |
| Regulatory pathway: | P65 NF-κB |
| R-AG-Pathway: | Downregulation |
| Pathway experiment: | Immunofluorescence//Immunoblotting |
| Pathway description: | We found that MFG-E8 treatment rescued the phosphorylation of p65 NF-κB signaling, while neutralizing MFG-E8 significantly enhanced p65 phosphorylation both in cartilage and in synovium post OA surgery. We found that the NF-κB pathway inhibitor JSH-23 partially reduced MFG-E8 loss-induced expression of P53, P21 and P16 in murine primary chondrocytes, and reduced the enhancing tendency of M1 macrophages caused by MFG-E8 deficiency. While NF-κB pathway activator phorbol 12-myristate 13-acetate (PMA) dismissed the inhibition of catabolism and senescence in chondrocytes, and decreased the M2 macrophage polarization induced by rmMFG-E8 . |
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