APPLICATION OF CARTILAGE EXTRACELLULAR MATRIX FOR ENHANCING THE THERAPEUTIC EFFICACY OF RHEUMATOID ARTHRITIS DRUG

Not scheduled
20m
ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków

Speaker

Seo, Jeong-woo (Pukyong National University )

Description

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and intra-articular cell infiltration. Currently, RA is still incurable, and treatment is aimed at relieving symptoms. Therefore, RA patients must be taken drugs continuously. Methotrexate (MTX) has been used for the treatment of RA since the 1980s and is the most used drug among disease-modifying anti-rheumatic drugs (DMARDs). These drugs can delay the progression of RA by effectively inhibiting cell proliferation and inflammation. However, various side effects such as nausea and diarrhea exist and the treatment effect of the drug decreases when taken for a long time. So, it must take a high-dose drug or in combination with other DMARDs for the treatment of RA. Native cartilage is a representative avascular tissue and consists of mainly collagen and glycosaminoglycan. We extracted the porcine cartilage extracellular matrix (CECM). Many papers were known to various tissue-derived extracellular matrix can modulate inflammatory environment. So far, researchers have been applied tissue-derived extracellular matrix to the treatment for degenerative and immune diseases. The hypothesis is that low-dose MTX with CECM can have a synergistic therapeutic effect on the RA animal model. To prove it, this study aim was to evaluate the CECM as a treatment CECM biomaterial. The experimental group was divided with Normal, Inflammation, 88μM MTX (high-dose), 44μM MTX with CECM, 11μM MTX (low-dose) with CECM, 2% CECM alone. In the results, human synovial cell (SW 982) in the high-dose MTX group showed the cytotoxicity, but low-dose MTX with CECM and 2% CECM alone groups did not showed the cytotoxicity based on cell proliferation assay. Regarding immune cell response, low-dose MTX with CECM group showed the depression of mouse macrophage cell (RAW 264.7) activation and proliferation like high-dose MTX. In addition, expressions related inflammatory cytokine genes had been also suppressed by treatment, both high-dose MTX and low-dose MTX with CECM. In conclusion, the low-dose MTX with CECM showed similar therapeutic effects to the high-dose MTX. It means we could reduce the side effects of high concentration MTX currently used for RA treatment. We can expect that suggested drug supporting biomaterial using cartilage ECM can provide conveniences, such as reducing the dosing interval and drug volume to RA patients.

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