BMSC-Derived Exosomes Ameliorate Osteoarthritis by Inhibiting Pyroptosis of Cartilage via Delivering miR-326 Targeting HDAC3 and STAT1//NF-κB p65 to Chondrocytes

Figure 4

Exosomes extracted from miR-326-overexpressed BMSCs significantly inhibited pyroptosis, HDAC3 expression, and STAT1/NF-κB p65 signaling pathway activation in OA chondrocytes, while silencing miR-326 had the opposite effect. (a) Exosomes extracted from miR-326-overexpressed BMSCs significantly promoted proliferation of OA chondrocytes, while silencing miR-326 had the opposite effect; (b) exosomes extracted from miR-326-overexpressed BMSCs significantly promoted migration of OA chondrocytes, while silencing miR-326 had the opposite effect; (c) exosomes extracted from miR-326-overexpressed BMSCs significantly increased the mRNA levels of chondrogenic specific genes (COL2A1, SOX9, Agg, and Prg4) in OA chondrocytes, while silencing miR-326 had the opposite effect; (d) exosomes extracted from miR-326-overexpressed BMSCs significantly decreased the levels of proinflammatory factors (IL-1β, IL-18, IL-6, and TNF-α) in OA chondrocytes, while silencing miR-326 had the opposite effect; (e) exosomes extracted from miR-326-overexpressed BMSCs significantly decreased DNA-binding activity of NF-κB p65 in OA chondrocytes, while silencing miR-326 had the opposite effect; (f) exosomes extracted from miR-326-overexpressed BMSCs significantly decreased Caspase-1 activity in OA chondrocytes, while silencing miR-326 had the opposite effect; (g) immunofluorescence results showed that exosomes extracted from miR-326-overexpressed BMSCs significantly decreased the levels of GSDMD and cl-Caspase-1 in OA chondrocytes, while silencing miR-326 had the opposite effect; (h) Western blot results showed that exosomes extracted from miR-326-overexpressed BMSCs significantly decreased the level of HDAC3 and activated the STAT1/NF-κB p65 signaling pathway in OA chondrocytes, while silencing miR-326 had the opposite effect; (i) Western blot results showed that exosomes extracted from miR-326-overexpressed BMSCs significantly decreased the levels of pyroptosis-related proteins (NLRP3, ASC, GSDMD, Caspase-1, IL-1β, and IL-18) in OA chondrocytes, while silencing miR-326 had the opposite effect; , .

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