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

Figure 7

BMSCs exosomal deliver miR-326 to cartilage and inhibit cartilage pyroptosis via activating STAT1 by targeting HDAC3. (a) BMSC-Exos incubation reversed the reduction of ICRS scores induced by OA; (b) HE staining results of cartilage tissue in each group, ; (c): Safranin-O/Fast Green staining results of cartilage tissue in each group, ; (d) expression levels of miR-326, HDAC3, and chondrogenic-specific genes (COL2A1, SOX9, Agg, and Prg4); mRNAs in OA chondrocytes of each group and BMSC-Exos incubation reversed the down-regulated mRNA level of chondrogenic-specific genes in cartilage induced by OA; BMSC-Exos with overexpression of miR-326 had a more significant effect; (e) BMSC-Exos incubation counteracted the increase levels of proinflammatory factors (IL-1β, IL-18, IL-6, and TNF-α) in cartilage induced by OA, and BMSC-Exos with overexpression of miR-326 had a more significant effect; (f) BMSC-Exos incubation counteracted the increase of DNA-binding activity of NF-κB p65 in cartilage induced by OA, and BMSC-Exos with overexpression of miR-326 had a more significant effect; (g) BMSC-Exos incubation counteracted the increase of Caspase-1 activity in cartilage induced by OA, and BMSC-Exos with overexpression of miR-326 had a more significant effect; (h) Immunofluorescence results showed that BMSC-Exos incubation counteracted the increase levels of GSDMD and cleaved Caspase-1 in cartilage induced by OA, and BMSC-Exos with overexpression of miR-326 had a more significant effect, ; (i) Western blot results showed that BMSC-Exos incubation counteracted the repression of STAT1/NF-κB p65 signaling pathway in cartilage induced by OA, and BMSC-Exos with overexpression of miR-326 had a more significant effect; (j) Western blot results showed that BMSC-Exos incubation counteracted the increase levels of pyroptosis-related proteins (NLRP3, ASC, GSDMD, Caspase-1, IL-1β, and IL-18) in cartilage induced by OA, and BMSC-Exos with overexpression of miR-326 had a more significant effect; , .

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