The Effect of Glutathione-Supplemented Hyaluronan on Osteoarthritis Synoviocytes

退化性關節炎在近年來，被認為是一種非典型的發炎疾病。而穀胱甘肽是一種擁有抗發炎效果的強抗氧化劑，可以保護細胞免受活性氧如自由基和過氧化物的傷害。本論文的目的為探討玻尿酸加入穀胱甘肽對於體外退化性關節炎模式之影響。將0.1mg/ml 的玻尿酸混合不同濃度的穀胱甘肽(5%, 10% 及 20%)，然後作用於從退化性關節炎的病人身上所取出的滑囊細胞，並由即時聚合酶鏈鎖反應檢測與退化性關節炎相關的基因，包括TNF-α, IL-6, MMP-3 和 TIMP-1之基因表現差異。結果發現玻尿酸混合20%穀胱甘肽可以降低一些對關節不好的降解性基因的表現，例如： TNF-α，MMP3。此外，混合20%穀胱甘肽的玻尿酸可以促進對關節有益的基因表現，例如：IL-6，TIMP-1。經由實驗結果，我們認為玻尿酸混合穀胱甘肽作為關節內注射劑有可能可以應用於減輕退化性關節炎之症狀。Osteoarthritis (OA) is recently recognized as a “non-classical” inflammatory disease. Glutathione (GSH), an antioxidant, has been shown to have an anti-inflammatory effect on protecting cells from reactive oxygen species such as free radicals and peroxides. This study is to examine the effects of hyaluronic acid (HA) supplemented with GSH on expression of four OA-related factors in fibroblast-like synoviocytes (FLSs) from five patients with OA. 0.1mg/ml of HA (Ostenil®) supplemented with different weight percent (5%, 10% and 20%) GSH were co-cultured with FLSs. The gene expression and protein production of OA-related factors, such as TNF-α, IL-6, MMP-3 and TIMP-1 were evaluated by real-time quantitative PCR. The gene expression of TNF-α and MMP-3 were found decreased significantly in every group. TIMP-1 was increased when HA supplemented with GSH in weight percent 5% and 20%. HA supplemented with GSH in weight percent 20% has showed significantly effect on regulating these factors. It had attenuated TNF-α, MMP-3 and up-regulated TIMP-1, IL-6 mRNA expression. We suggest that intra-articular injection of HA supplemented with GSH may be feasible for relieve symptoms of knee osteoarthritis