Details

Autor(en) / Beteiligte

• Wang, C.-T.
• Lin, Y.-T.
• Chiang, B.-L.
• Lin, Y.-H.
• Hou, S.-M.

Titel

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

Ist Teil von

• Osteoarthritis and cartilage, 2006-12, Vol.14 (12), p.1237-1247

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.