title: l-Glutathione enhances antioxidant capacity of hyaluronic acid and modulates expression of pro-inflammatory cytokines in human fibroblast-like synoviocytes.
abstract: Intra-articular injection of hyaluronic acid (HA) has been widely accepted for the treatment of osteoarthritis (OA) in early stage. l-Glutathione (GSH), an antioxidant, has an anti-inflammatory effect on protecting cells from reactive oxygen species and reactive nitrogen species (ROS/RNS). In this study, the therapeutic effects of HA (0.1%) supplemented with GSH (0, 5, 10, and 20% in weight ratios to HA) on human fibroblast-like synoviocytes (FLSs) were evaluated. The results showed that cell morphology and glycosaminoglycan production of FLSs were not changed under treatments. However, the addition of HA + 20% GSH significantly decreased cell survival (p < 0.001) relative to other groups. Relative to un-stimulated FLSs, interleukin-1 beta (IL-1β) stimulation significantly decreased the total antioxidant capacity (p < 0.001) of cells. The antioxidant capacity was restored and the intracellular ROS/RNS was decreased in HA or HA + GSH-treated FLSs. Real-time PCR analysis revealed the mRNA levels of IL-1β, tumor necrosis factor-alpha, and matrix metalloproteinase-3 were down-regulated significantly (all p < 0.05) when FLSs cultured in HA or HA + GSH. IL-6 mRNA expressions were down-regulated significantly in HA and HA + 5% GSH groups (both p < 0.05) but up-regulated when HA supplemented with 10% and 20% GSH (both p < 0.01). In addition, the protein levels of IL-1β were further decreased with significant differences (both p < 0.05) in the HA + 10% GSH and HA + 20% GSH groups when compared to FLSs cultured in normal medium. In conclusion, HA supplemented with GSH improves antioxidant capacity and modulates pro-inflammatory cytokines expressions in FLSs. GSH has the potential to augment the effect of viscosupplementation using HA on OA patients. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2071-2079, 2016.
authors.affiliation: School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, 11031, Taiwan.|Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Kai-Chiang
authors.initials: KC
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 10002, Taiwan.|Department of Orthopedics, En Chu Kong Hospital, New Taipei City, 23702, Taiwan.
authors.forename: Chang-Chin
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Materials Science and Engineering, University of Sheffield, Sheffield, S10 2TN, United Kingdom.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Sumi
authors.affiliation: Department of Sports Medicine, College of Health Care, China Medical University, Taichung, 40402, Taiwan.|Department of Orthopedics, An-Nan Hospital, China Medical University, Tainan, 70965, Taiwan.
authors.forename: Teng-Le
authors.initials: TL
authors.lastname: Huang
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D005978:Glutathione / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000070918:Synoviocytes / Q000166:cytology* / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D006025:Glycosaminoglycans; D018836:Inflammation Mediators; D012333:RNA, Messenger; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D006820:Hyaluronic Acid; D005978:Glutathione
keywords: fibroblast-like synoviocyte; glutathione; hyaluronic acid; osteoarthritis