miR ‐219a‐5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3

Autor: Qiang Wang, Pei‐Yan Huang, Jun‐Guo Wu, Tie‐Qi Zhang, Ling‐Feng Li, Liang‐Da Huang, Yue‐Ming Yu, Ming‐hai Wang, Jun He
Rok vydání: 2022
Předmět:
Zdroj: Environmental Toxicology. 37:2673-2682
ISSN: 1522-7278
1520-4081
DOI: 10.1002/tox.23627
Popis: This work was to identify the function and mechanism of miR-219a-5p in regulating knee osteoarthritis (KOA).Rat fibroblast-like synoviocytes (FLSs) were isolated to construct KOA cell model by lipopolysaccharide and adenosine triphosphate treatment. miR-219a-5p and FBXO3 expression in FLSs was modulated by transfection. Flow cytometry was executed to research FLSs apoptosis. Caspase-1 and IL-1β expression in FLSs was researched by immunofluorescence. The binding between miR-219a-5p and FBXO3 was identified by dual luciferase reporter gene assay. KOA rat model and miR-219a-5p up-modulation KOA rat model were constructed. Step size of rats was analyzed. Knee joints of rats were experienced Safranin O-fast green staining to evaluate the knee joint injury. FBXO3, pyroptosis-associated proteins, and IL-1β and IL-18 expression in FLSs and articular cartilage tissues of rats were assessed by Western blot, qRT-PCR and Enzyme-linked immunosorbent assay.KOA cell model had higher apoptosis percentage, expression of pyroptosis-associated proteins, and IL-1β and IL-18 level. miR-219a-5p up-modulation decreased the above indicators, whereas miR-219a-5p down-modulation increased the above indicators. FBXO3 expression was directly repressed by miR-219a-5p. Loss of FBXO3 suppressed the above indicators. FBXO3 counteracted the suppression of miR-219a-5p on the above indicators. miR-219a-5p agomir attenuated knee joint injury, increased step size of KOA rats, and reduced FBXO3, pyroptosis-associated proteins and level of IL-1β and IL-18 in the articular cartilage tissues of KOA rats.miR-219a-5p suppressed the pyroptosis in KOA by inactivating the NLRP3 signaling via targeting FBXO3, which might be a promising target for ameliorating KOA in the clinic.
Databáze: OpenAIRE
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