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Effects of 1α,25dihydroxyvitamin D3 on matrix metalloproteinase and prostaglandin E2production by cells of the rheumatoid lesion

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1α,25dihydroxyvitamin D3 (1α,25D3), the active form of vitamin D3, through its interaction with intracellular vitamin D receptors (VDRs), is reported to effect a variety of anabolic and catabolic events, especially in bone and cartilage tissues [1,2,3]. VDRs were demonstrated in most specimens of cartilage-pannus junction, within synovial pannus tissue, and by chondrocytes often close to the erosive lesion [4]. In vitro studies have examined the effects of 1α,25D3 on rheumatoid synovial explants and monolayer cultures of rheumatoid synovial fibroblasts (RSFs) and human articular chondrocytes (HACs) with respect to MMP and prostaglandin E2 (PGE2) production. Explant cultures exposed to 1α 25D3 showed little change in the production of matrix metalloproteinase (MMP)-1 and MMP-3, but MMP-9 was markedly suppressed. The expression of MMP-1, -3, and -9 by RSFs was unaffected by 1α,25D3 alone, but when stimulated with IL-1β the resultant increase was significantly inhibited (~ 60%) by 1α,25D3. Conversely, although treatment of HACs with 1α,25D3 alone had little effect on MMP production, the increase in MMP-1 and -3 seen with IL-1β stimulation was further enhanced by the simultaneous addition of 1α,25D3. Such observations demonstrate that IL-1-activated RSFs and HACs respond differently to 1α,25D3 exposure, and that the latter has different effects on the regulatory pathways of specific MMPs. PGE2 production by RSFs stimulated with IL-1β was also significantly reduced (by up to 70%) following the simultaneous addition of 1α,25D3, a suppression not observed in IL-1β-stimulated HAC cultures. Moreover, when RSFs were preincubated with 1α,25D3 prior to the addition of IL-1β, subsequent PGE2 production was more markedly suppressed — an observation suggesting either that 1α,25D3 interferes with the IL-1β signalling pathway or by its recognised immunosuppressive functions reported for other cells. Immunohistochemical studies of the rheumatoid lesion have demonstrated similar distributions for the expression of VDRs and specific MMPs in situ — observations that further suggest that 1α,25D3 may be involved in the modulation of MMP and prostanoid expression of the rheumatoid lesion.

Work supported by the Arthritis Research Campaign, United Kingdom.

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Tetlow, L.C., Woolley, D.E. Effects of 1α,25dihydroxyvitamin D3 on matrix metalloproteinase and prostaglandin E2production by cells of the rheumatoid lesion. Arthritis Res Ther 1, S21 (1999) doi:10.1186/ar35

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