l-Glutathione enhances antioxidant capacity of hyaluronic acid and modulates expression of pro-inflammatory cytokines in human fibroblast-like synoviocytes

K.-C. Yang, Chang Chin Wu, Wei Yu Chen, S. Sumi, Teng Le Huang

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17 Citations (Scopus)


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. © 2016 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)2071-2079
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Issue number8
Publication statusPublished - 2016


  • fibroblast-like synoviocyte
  • glutathione
  • hyaluronic acid
  • osteoarthritis
  • Antioxidants
  • Cell culture
  • Cells
  • Cytology
  • Enzyme activity
  • Fibroblasts
  • Organic acids
  • Peptides
  • Polymerase chain reaction
  • Tissue
  • Glutathiones
  • Intra-articular injection
  • Matrix-metalloproteinase-3
  • Pro-inflammatory cytokines
  • Synoviocytes
  • Total antioxidant capacity
  • Tumor necrosis factor alpha
  • Hyaluronic acid


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