Open AccessAntiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model of erosive arthritis
Author(s) -
Blüml Stephan,
Binder Nikolaus B.,
Niederreiter Birgit,
Polzer Karin,
Hayer Silvia,
Tauber Stefanie,
Schett Georg,
Scheinecker Clemens,
Kollias George,
Selzer Edgar,
Bilban Martin,
Smolen Josef S.,
SupertiFurga Giulio,
Redlich Kurt
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27399
Subject(s) - tumor necrosis factor alpha , haematopoiesis , osteoclast , arthritis , immunology , inflammation , bone marrow , cancer research , medicine , hematopoietic growth factor , biology , stem cell , microbiology and biotechnology , receptor
Objective To investigate the mechanisms leading to the influx of inflammatory hematopoietic cells into the synovial membrane and the role of tumor necrosis factor receptor I (TNFRI) and TNFRII in this process in an animal model of rheumatoid arthritis (RA). Methods We performed bone marrow transplantations in human TNF–transgenic mice using hematopoietic cells from wild‐type, TNFRI −/− , TNFRII −/− , and TNFRI/II −/− mice as donors and assessed the severity of arthritis histologically. Generation of osteoclasts from the different genotypes was analyzed in vitro and in vivo. Apoptosis was analyzed using annexin V staining as well as TUNEL assays. Results Despite lacking responsiveness to TNF in their hematopoietic compartment, mice not only developed full‐blown erosive arthritis but even showed increased joint destruction when compared with mice with a TNF‐responsive hematopoietic compartment. We demonstrated different roles of the 2 different TNFRs in the regulation of these processes. The absence of TNFRI on hematopoietic cells did not affect joint inflammation but markedly attenuated erosive bone destruction via reduced synovial accumulation of osteoclast precursors. In contrast, the absence of TNFRII on hematopoietic cells increased joint inflammation as well as erosive bone destruction via the regulation of osteoclast precursor apoptosis. Conclusion Our findings indicate that selective blockade of TNFRI, leaving the antiinflammatory effects of TNFRII unaltered instead of unselectively blocking TNF, might be advantageous in patients with RA.