| TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with osteoprotegerin. | |
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MedLine Citation:
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PMID: 21162099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: TSG-6 (the product of tumor necrosis factor [TNF]-stimulated gene 6) has a potent inhibitory effect on RANKL-mediated bone erosion. The aim of this study was to compare the activity of TSG-6 with that of osteoprotegerin (OPG) and to investigate its role as an autocrine modulator of cytokine-mediated osteoclast formation/activation. We also determined TSG-6 expression in inflammatory joint disease. METHODS: The effects of TSG-6, OPG, and the inflammation mediators TNFα, interleukin-1 (IL-1), and IL-6 on the formation of osteoclasts from peripheral blood mononuclear cells and synovial fluid (SF) macrophages were determined by tartrate-resistant acid phosphatase staining. Lacunar resorption and filamentous actin ring formation were measured as indicators of osteoclast activity. The amount of TSG-6 in culture media or SF was quantified by enzyme-linked immunosorbent assay, and expression of TSG-6 in synovial tissue was assessed by immunohistochemistry. RESULTS: TSG-6 acted in synergy with OPG to inhibit RANKL-mediated bone resorption and was produced by osteoclast precursors and mature osteoclasts in response to TNFα, IL-1, and IL-6. Expression of TSG-6 correlated with inhibition of lacunar resorption; this effect was ameliorated by an anti-TSG-6 antibody. The level of TSG-6 protein was determined in SF from patients with various arthritides; it was highest in patients with inflammatory conditions such as rheumatoid arthritis, in which it correlated with the amount of TSG-6 immunostaining in the synovium. TSG-6 inhibited the activation but not the formation of osteoclasts from SF macrophages. CONCLUSION: In the presence of inflammatory cytokines, osteoclasts produced TSG-6 at concentrations that are sufficient to inhibit lacunar resorption. This may represent an autocrine mechanism to limit the degree of bone erosion during joint inflammation. |
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Authors:
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David J Mahoney; Catherine Swales; Nicholas A Athanasou; Michele Bombardieri; Costantino Pitzalis; Karolina Kliskey; Mohammed Sharif; Anthony J Day; Caroline M Milner; Afsie Sabokbar |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 63 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-31 Completed Date: 2011-05-23 Revised Date: 2011-12-01 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 1034-43 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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University of Oxford, Oxford, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Arthritis, Psoriatic / pathology, physiopathology Arthritis, Rheumatoid / pathology, physiopathology Autocrine Communication / physiology* Bone Resorption / pathology, physiopathology* Cell Adhesion Molecules / pharmacology* Cell Differentiation / drug effects Cells, Cultured Female Humans Interleukin-1 / pharmacology Interleukin-6 / pharmacology Macrophages / drug effects, pathology Male Osteoarthritis, Knee / pathology, physiopathology Osteoclasts / drug effects*, pathology Osteoprotegerin / pharmacology* Tumor Necrosis Factor-alpha / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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16539//Arthritis Research UK; 17590//Arthritis Research UK; 18237//Arthritis Research UK; 18358//Arthritis Research UK; 18399//Arthritis Research UK |
| Chemical | |
Reg. No./Substance:
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0/Cell Adhesion Molecules; 0/Interleukin-1; 0/Interleukin-6; 0/Osteoprotegerin; 0/TNFAIP6 protein, human; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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