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    Vitamin D receptor regulates TNF-mediated arthritis

    Ann Rheum Dis. 2011 Mar 17. [Epub ahead of print]

    These authors demonstrate that the arthritis in mice that overexpress human tumor necrosis factor (hTNF) is increased if the hTNF-overexpressing mice are crossed with vitamin D receptor (VDR) deficient mice. VDR deficient monocytes also had an increased capacity to differentiate into osteoclasts. These data argue that vitamin D signaling is anti-inflammatory in this mouse model.
    Authors: Zwerina K, Baum W, Axmann R, et. al

    OBJECTIVE: /st> 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: /st> 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: /st> 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: /st> 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.

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