Details

Autor(en) / Beteiligte

• Zwerina, Karin
• Baum, Wolfgang
• Axmann, Roland
• Heiland, Gisela Ruiz
• Distler, Jörg H
• Smolen, Josef
• Hayer, Silvia
• Zwerina, Jochen
• Schett, Georg

Titel

Vitamin D receptor regulates TNF-mediated arthritis

Ist Teil von

• Annals of the rheumatic diseases, 2011-06, Vol.70 (6), p.1122-1129

Ort / Verlag

London: BMJ Publishing Group Ltd and European League Against Rheumatism

Erscheinungsjahr

2011

Quelle

BMJ Journals Archiv - DFG Nationallizenzen

Beschreibungen/Notizen

• Objective Reduced vitamin D intake has been linked to increased susceptibility to develop rheumatoid arthritis (RA) and vitamin D deficiency is associated with increased disease activity in RA patients. The pathophysiological role of vitamin D in joint inflammation is, however, unclear. Methods To determine the influence of absent vitamin D signalling in chronic arthritis, vitamin D receptor (VDR)-deficient mice were crossed with human tumour necrosis factor (TNF) transgenic mice (hTNFtg), which spontaneously develop chronic arthritis. Results Clinical signs and symptoms of chronic arthritis were aggravated in hTNFtg mice lacking functional VDR signalling. Moreover, synovial inflammation was clearly increased in VDR−/−hTNFtg mice as compared to hTNFtg mice and was associated with an increased macrophage influx in inflamed joints. In vitro, VDR-deficient monocytes were proinflammatory and hyper-responsive to TNF stimulation associated with prolonged mitogen-activated protein kinase activation and cytokine secretion. Also, VDR−/− monocytes showed enhanced potential to differentiate into bone resorbing osteoclasts in vitro. In line, VDR−/−hTNFtg mice had significantly increased cartilage damage and synovial bone erosions. Conclusions VDR plays an important role in limiting the inflammatory phenotype in a mouse model of RA. Absent VDR signalling causes a proinflammatory monocyte phenotype associated with increased inflammation, cartilage damage and bone erosion.