Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovial Fibroblasts
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....
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| creator | Watanabe, Tatsuo Takahashi, Nobunori Hirabara, Shinya Ishiguro, Naoki Kojima, Toshihisa |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0153142 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0153142</identifier><identifier>PMID: 27054952</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Arthritis ; Arthritis, Rheumatoid - genetics ; Arthritis, Rheumatoid - metabolism ; Biocompatibility ; Biology and Life Sciences ; Biomedical materials ; Bones ; CD44 antigen ; Cell adhesion ; Cell Differentiation - drug effects ; Cells, Cultured ; Clinical trials ; Complications and side effects ; Cytokines ; Dosage and administration ; Drug therapy ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Gene Expression Regulation - drug effects ; Humans ; Hyaluronic acid ; Hyaluronic Acid - pharmacology ; Immune system ; Intercellular adhesion molecule 1 ; Joint surgery ; Ligands ; Lipopolysaccharides ; Medicine ; Medicine and Health Sciences ; Molecular weight ; Osteoclastogenesis ; Osteoclasts ; Pathogenesis ; Proteins ; RANK Ligand - genetics ; RANK Ligand - metabolism ; Rankings ; Research and Analysis Methods ; Rheumatism ; Rheumatoid arthritis ; Rheumatology ; Signal transduction ; Signaling ; Studies ; Surgery ; Synovial Membrane - cytology ; Synovial Membrane - drug effects ; Synovial Membrane - metabolism ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; TRANCE protein ; Tumor necrosis factor-TNF ; University graduates</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0153142-e0153142</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Watanabe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Biocompatibility</subject><subject>Biology and Life Sciences</subject><subject>Biomedical materials</subject><subject>Bones</subject><subject>CD44 antigen</subject><subject>Cell adhesion</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Clinical trials</subject><subject>Complications and side effects</subject><subject>Cytokines</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Hyaluronic acid</subject><subject>Hyaluronic Acid - pharmacology</subject><subject>Immune system</subject><subject>Intercellular adhesion molecule 1</subject><subject>Joint surgery</subject><subject>Ligands</subject><subject>Lipopolysaccharides</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Molecular weight</subject><subject>Osteoclastogenesis</subject><subject>Osteoclasts</subject><subject>Pathogenesis</subject><subject>Proteins</subject><subject>RANK Ligand - genetics</subject><subject>RANK Ligand - metabolism</subject><subject>Rankings</subject><subject>Research and Analysis Methods</subject><subject>Rheumatism</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatology</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Studies</subject><subject>Surgery</subject><subject>Synovial Membrane - cytology</subject><subject>Synovial Membrane - drug effects</subject><subject>Synovial Membrane - metabolism</subject><subject>Toll-Like Receptor 4 - genetics</subject><subject>Toll-Like Receptor 4 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watanabe, Tatsuo</au><au>Takahashi, Nobunori</au><au>Hirabara, Shinya</au><au>Ishiguro, Naoki</au><au>Kojima, Toshihisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovial Fibroblasts</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-07</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0153142</spage><epage>e0153142</epage><pages>e0153142-e0153142</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27054952</pmid><doi>10.1371/journal.pone.0153142</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Arthritis Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - metabolism Biocompatibility Biology and Life Sciences Biomedical materials Bones CD44 antigen Cell adhesion Cell Differentiation - drug effects Cells, Cultured Clinical trials Complications and side effects Cytokines Dosage and administration Drug therapy Fibroblasts Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Gene Expression Regulation - drug effects Humans Hyaluronic acid Hyaluronic Acid - pharmacology Immune system Intercellular adhesion molecule 1 Joint surgery Ligands Lipopolysaccharides Medicine Medicine and Health Sciences Molecular weight Osteoclastogenesis Osteoclasts Pathogenesis Proteins RANK Ligand - genetics RANK Ligand - metabolism Rankings Research and Analysis Methods Rheumatism Rheumatoid arthritis Rheumatology Signal transduction Signaling Studies Surgery Synovial Membrane - cytology Synovial Membrane - drug effects Synovial Membrane - metabolism Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - metabolism Toll-like receptors TRANCE protein Tumor necrosis factor-TNF University graduates |
| title | Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovial Fibroblasts |
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