Document Detail


Tumor necrosis factor-inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor-driven model of rheumatoid arthritis.
MedLine Citation:
PMID:  23280418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate how tumor necrosis factor (TNF)-inhibiting therapy affects bone destruction and inflammation in a TNF-driven mouse model of rheumatoid arthritis.
METHODS: In order to evaluate the influence of TNF on osteoclastogenesis in vitro, different concentrations of TNF were added to spleen cell-derived monocytes in the absence or presence of different concentrations of RANKL. In addition, the effects of TNF inhibition on osteoclast precursors as well as local bone destruction in vivo were assessed by treating TNF-transgenic mice with different doses of adalimumab.
RESULTS: TNF stimulated osteoclastogenesis mainly by increasing the number of osteoclast precursor cells in vitro. This TNF effect was independent of the presence of RANKL. In the hTNF-transgenic mouse model of destructive arthritis, low-dose TNF-inhibiting therapy with adalimumab had no effect on synovial inflammation but significantly inhibited local bone destruction and the generation of osteoclasts. This inhibition was accompanied by a reduction in the number of c-Fms-positive osteoclast precursor cells in the bone marrow and a reduction of the osteoclast precursor pools in the blood and inflamed synovial membrane of hTNF-transgenic mice.
CONCLUSION: Low-dose TNF-inhibiting therapy significantly reduces bone erosions by reducing the number of circulating and joint-invading osteoclast precursors. This effect is uncoupled from its antiinflammatory action.
Authors:
Nikolaus B Binder; Antonia Puchner; Birgit Niederreiter; Silvia Hayer; Harald Leiss; Stephan Blüml; Roman Kreindl; Josef S Smolen; Kurt Redlich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-04-24     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  608-17     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Affiliation:
Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal, Humanized / pharmacology*
Antirheumatic Agents / pharmacology
Arthritis, Rheumatoid / drug therapy*,  immunology,  pathology
Bone and Bones / drug effects,  pathology
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Osteoclasts / drug effects,  pathology
RANK Ligand / genetics
Receptor, Macrophage Colony-Stimulating Factor / genetics
Stem Cells / drug effects,  pathology
Synovial Membrane / drug effects,  pathology
Synovitis / drug therapy*,  immunology,  pathology
Tumor Necrosis Factor-alpha / antagonists & inhibitors*,  genetics,  pharmacology*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; 0/Antirheumatic Agents; 0/RANK Ligand; 0/Tnfsf11 protein, mouse; 0/Tumor Necrosis Factor-alpha; EC 2.7.10.1/Receptor, Macrophage Colony-Stimulating Factor; FYS6T7F842/adalimumab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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