High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis
Journal
Osteoarthritis and Cartilage
Journal Volume
14
Journal Issue
12
Pages
1237-1247
Date Issued
2006
Author(s)
Abstract
Objective: Activated synoviocytes play important roles in the progression of human osteoarthritis (OA). Intra-articular injection of high molecular weight hyaluronic acid (HMW-HA) has been used as viscosupplementation for knee OA but its effect on synoviocytes remains undisclosed. This study aims to investigate the effects of HMW-HA on the gene expression of 16 OA-associated cytokines and enzymes, including interleukin (IL)-1β, IL-6, IL-8, leukemia inhibitory factor (LIF), tumor necrosis factor (TNF)-α, TNF-α converting enzyme (TACE), matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, aggrecanase-1, aggrecanase-2, and inducible nitric oxide synthase (iNOS), in fibroblast-like synoviocytes (FLS) from patients with early stage OA. Method: Synovial fluid-derived FLS were obtained from the knees of 15 patients with early stage OA. IL-1-stimulated or unstimulated FLS were cultured with or without the treatment of 600-800 kDa HMW-HA. Moreover, blocking experiments with anti-CD44 monoclonal antibodies (mAb) were used to examine the involvement of CD44 in HMW-HA effects. We designed and validated the real-time quantitative polymerase chain reaction (Q-PCR) assays with SYBR Green dyes for simultaneous quantification of the expression of the 16 genes. Results: HMW-HA down-regulated IL-8 and iNOS gene expression in unstimulated FLS and down-regulated aggrecanase-2 and TNF-α gene expression in IL-1-stimulated FLS. CD44 blocking inhibited the down-regulatory effects of HMW-HA on gene expression. Conclusion: HMW-HA may have a structure-modifying effect for OA by down-regulation of aggrecanase-2 in FLS. HMW-HA also has an anti-inflammatory effect by down-regulation of TNF-α, IL-8, and iNOS in FLS. These effects may be mediated through the interaction of CD44 and HMW-HA. ? 2006 OsteoArthritis Research Society International.
SDGs
Other Subjects
aggrecanase; aggrecanase 1; aggrecanase 2; artzdispo; collagenase 3; cytokine; enzyme; gelatinase A; gelatinase B; Hermes antigen; hyaluronic acid; inducible nitric oxide synthase; interleukin 1beta; interleukin 6; interleukin 8; interstitial collagenase; leukemia inhibitory factor; monoclonal antibody; stromelysin; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 2; tumor necrosis factor alpha; tumor necrosis factor alpha converting enzyme; unclassified drug; antiinflammatory activity; article; cell activation; clinical article; concentration response; controlled study; disease course; down regulation; drug effect; gene amplification; gene expression regulation; human; human cell; knee osteoarthritis; molecular weight; nucleotide sequence; phenotypic variation; priority journal; quantitative analysis; real time polymerase chain reaction; synovial fluid; synoviocyte; validation study; ADAM Proteins; Antigens, CD44; Cytokines; Dose-Response Relationship, Drug; Down-Regulation; Fibroblasts; Humans; Hyaluronic Acid; Interleukin-1; Interleukin-8; Molecular Weight; Nitric Oxide Synthase Type II; Osteoarthritis, Knee; Polymerase Chain Reaction; Synovial Fluid; Tumor Necrosis Factor-alpha
Type
journal article