Osteoarthritis (OA) is a disease characterized by the degradation of articular cartilage. Extracellular vesicles (EVs) are cargo-filled bodies that mediate intercellular communication and are influential in OA pathogenesis. This study utilized parallel methodologies to investigate whether EV signaling can be manipulated to combat OA. The first approach aimed to identify cells lines that produce EVs with therapeutic activity against OA, while the second introduced miRNA in EVs to induce cartilage regeneration. EVs derived from synovial fibroblasts (SFBs) induced further inflammation. Moreover, miRNA did not impact MMP-13 production. While SFB-EVs were pro-inflammatory, increasing the amount of MMP-13 present, human bone marrow-derived mesenchymal stem cell (BM-hMSC) EVs did not stimulate a change in MMP-13 production. Future studies should further characterize these results to maximize therapeutic impact.