IADR Abstract Archives
Reducing Inflammation and Cartilage Degeneration in TMJ Osteoarthritis Using MicroRNA Modulation
Objectives: We have demonstrated that microRNA (miR)-200c reduces IL-6, IL-8, and CCL-5, and miR-17 inhibition upregulates TGF-β receptor 2. Thus, miR-200c overexpression and miR-17 inhibition have potential uses as a therapeutic tool to reduce inflammation and cartilage degeneration in temporomandibular joint (TMJ) osteoarthritis (OA) by mediating proinflammatory mediators of cartilage degeneration and TGF-β signaling. The objective of this study is to test the effect of miR-200c overexpression and miR-17 inhibition on suppressing inflammation and cartilage degeneration in vitro and in vivo.
Methods: Plasmid DNA encoding miR-200c and plasmid-based miR-17 inhibitor (PMIS-miR-17) were transfected into human chondrocytes and synoviocytes. The proinflammatory mediators of cartilage degeneration in the cells with the miR-200c overexpression and miR-17 inhibition were quantitated after IL-1β treatment. In addition, plasmid miR-200c and PMIS-miR-17 were intra-articularly injected into mouse TMJs with unilateral partial discectomy, a mouse model of degenerative joint disease (DJD). The mice were euthanized after 1, 2 and 4 weeks post-operatively and the inflammation and cartilage degeneration of TMJ with different treatment were investigated.
Results: Overexpression of miR-200c and inhibition of miR-17 in human chondrocytes, synoviocytes, and mouse TMJ tissues were confirmed using real-time PCR after treatment with plasmid miR-200c and PMIS-miR-17, respectively. After exposure to IL-1β, proinflammatory mediators of cartilage degeneration, including IL-6, IL-8, MMP-9, and MMP-13, were down-regulated in the cells treated with miR-200c and PMIS-miR-17, compared to the cells treated with empty vectors. In addition, intra-articular injection of plasmid miR-200c and PMIS-miR-17 effectively reduced the proinflammatory mediators of cartilage degeneration in a mouse model for TMJ OA (TMJ discectomy).
Conclusions: These data demonstrated that miR-200c overexpression and miR-17 inhibition attenuate inflammation and cartilage degeneration, indicating their potential to be used for TMJ OA treatment.
Methods: Plasmid DNA encoding miR-200c and plasmid-based miR-17 inhibitor (PMIS-miR-17) were transfected into human chondrocytes and synoviocytes. The proinflammatory mediators of cartilage degeneration in the cells with the miR-200c overexpression and miR-17 inhibition were quantitated after IL-1β treatment. In addition, plasmid miR-200c and PMIS-miR-17 were intra-articularly injected into mouse TMJs with unilateral partial discectomy, a mouse model of degenerative joint disease (DJD). The mice were euthanized after 1, 2 and 4 weeks post-operatively and the inflammation and cartilage degeneration of TMJ with different treatment were investigated.
Results: Overexpression of miR-200c and inhibition of miR-17 in human chondrocytes, synoviocytes, and mouse TMJ tissues were confirmed using real-time PCR after treatment with plasmid miR-200c and PMIS-miR-17, respectively. After exposure to IL-1β, proinflammatory mediators of cartilage degeneration, including IL-6, IL-8, MMP-9, and MMP-13, were down-regulated in the cells treated with miR-200c and PMIS-miR-17, compared to the cells treated with empty vectors. In addition, intra-articular injection of plasmid miR-200c and PMIS-miR-17 effectively reduced the proinflammatory mediators of cartilage degeneration in a mouse model for TMJ OA (TMJ discectomy).
Conclusions: These data demonstrated that miR-200c overexpression and miR-17 inhibition attenuate inflammation and cartilage degeneration, indicating their potential to be used for TMJ OA treatment.