Vitamin D receptor regulates TNF-mediated arthritis

Language
en
Document Type
Article
Issue Date
2016-11-15
Issue Year
2011
Authors
Zwerina, Karin
Baum, Wolfgang
Axmann, Roland
Ruiz Heiland, Gisela
Distler, Jörg H.
Smolen, Josef
Hayer, Silvia
Zwerina, Jochen
Schett, Georg
Editor
Abstract

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.

Journal Title
Annals of the Rheumatic Diseases
Volume
70
Issue
6
Citation
Annals of the Rheumatic Diseases 70.6 (2011): S. 1122-1129. <http://ard.bmj.com/content/70/6/1122>
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