Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovial Fibroblasts.
Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovial Fibroblasts.
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DOI：
10.1371/journal.pone.0153142
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kojima T
中科院分区：
文献类型：
--
作者：
Watanabe T;Takahashi N;Hirabara S;Ishiguro N;Kojima T
Toll样受体（TLR）信号通路在类风湿性关节炎（RA）患者的滑膜成纤维细胞中被激活。核因子-κB受体激活因子（RANK）及其配体RANKL是参与RA破骨细胞分化和关节破坏的关键分子。透明质酸（HA）是一种主要的细胞外成分，也是一种重要的免疫调节剂。在这项研究中，我们表明，脂多糖（LPS）刺激显着增加RANKL表达通过TLR-4信号通路。我们还证明，HA抑制LPS诱导的RANKL表达，这是依赖于CD 44，但不是细胞间粘附分子-1（ICAM-1）。我们的研究为HA介导的TLR-4依赖性RANKL表达抑制提供了证据。这可能为治疗RA中破坏的关节骨和软骨提供替代靶点。
The Toll-like receptor (TLR) signaling pathway is activated in synovial fibroblast cells in patients with rheumatoid arthritis (RA). The receptor activator of nuclear factor-κB (RANK) and its ligand, RANKL, are key molecules involved in the differentiation of osteoclasts and joint destruction in RA. Hyaluronan (HA) is a major extracellular component and an important immune regulator. In this study, we show that lipopolysaccharide (LPS) stimulation significantly increases RANKL expression via a TLR-4 signaling pathway. We also demonstrate that HA suppresses LPS-induced RANKL expression, which is dependent on CD44, but not intercellular adhesion molecule-1 (ICAM-1). Our study provides evidence for HA-mediated suppression of TLR-4-dependent RANKL expression. This could present an alternative target for the treatment of destructed joint bones and cartilages in RA.