FOXQ1 inhibits the progression of osteoarthritis by regulating pyroptosis.

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-1ß-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.