(A). Trap staining assay in Raw264.7 cells untreated or treated for 6 days with 25μg/mL of MM-EVs, with 200 nM GSK2850163 (IRE1ι) and co-treated with MM-EVs and IRE1ι. (B). Representative images of TRAP+ Raw264.7 cells (original magnification 20×). (C). qRT-PCR analysis of Trap and Cathk in Raw264.7 cells treated for 6 days with 25 μg/mL of MM-EVs, with 200 nM GSK2850163 (IRE1ι) and co-treated with MM-EVs and IRE1ι. (D). ELISA assay of mMMP9 protein levels in conditioned medium of Raw264.7 cells treated for 6 days with 25 μg/mL of MM-EVs, with 200 nM GSK2850163 (IRE1ι) and co-treated with MM-EVs and IRE1ι. The statistical significance of the differences was analyzed using a Dunnett’s test (treated Groups vs. Untreated Group) (* p-value< 0.05, *** p-value < 0.0005, ns not significant).