Article ; Online: FOXQ1 inhibits the progression of osteoarthritis by regulating pyroptosis.
Aging
2024 Volume 16, Issue 6, Page(s) 5077–5090
Abstract: Background: Osteoarthritis (OA) is the most common age-related joint disease, and the NLRP3-induced pyroptosis has been demonstrated in its progression. The upstream molecules or specific mechanisms controlling NLRP3 and pyroptosis in OA remain unclear.! ...
Abstract | Background: Osteoarthritis (OA) is the most common age-related joint disease, and the NLRP3-induced pyroptosis has been demonstrated in its progression. The upstream molecules or specific mechanisms controlling NLRP3 and pyroptosis in OA remain unclear. Methods: Transcriptome sequencing was performed in the OA mice model, and the expression levels of differentially expressed genes were assessed by qRT-PCR. The cell model was constructed by IL-1β-induced ATDC5 cells. The cell proliferation was examined using CCK-8 assay, and apoptosis was tested using flow cytometry. Western blot was used in protein inspection, and ELISA was used in inflammatory response evaluation. Results: Compared with the control group, there were 229 up-regulated and 32 down-regulated genes in model group. We detected that FOXQ1 was down-regulated in the OA mice model, improved proliferation, and restrained apoptosis of chondrocytes. Over-expression of FOXQ1 could inhibit pyroptosis-related proteins and inflammatory cytokines, containing NLRP3, Caspase-1, GSDMD, IL-6, IL-18, and TNF-α, and in contrast, FOXQ1 silencing exerted the opposite trend. Conclusions: FOXQ1 may inhibit OA progression via down-regulating NLRP3-induced pyroptosis in the present study. |
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MeSH term(s) | Animals ; Mice ; Apoptosis/genetics ; Caspase 1/metabolism ; Disease Models, Animal ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Osteoarthritis/genetics ; Pyroptosis |
Chemical Substances | Caspase 1 (EC 3.4.22.36) ; NLR Family, Pyrin Domain-Containing 3 Protein ; Foxq1 protein, mouse |
Language | English |
Publishing date | 2024-03-19 |
Publishing country | United States |
Document type | Journal Article |
ISSN | 1945-4589 |
ISSN (online) | 1945-4589 |
DOI | 10.18632/aging.205600 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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