Molecular Medicine

, Volume 18, Issue 2, pp 194–200 | Cite as

The Vitamin D Receptor Regulates Rheumatoid Arthritis Synovial Fibroblast Invasion and Morphology

  • Teresina Laragione
  • Anish Shah
  • Pércio S. Gulko
Research Article


Serum levels of vitamin D levels are commonly reduced in patients with rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. We recently identified a new vitamin D receptor transcriptional signature in synovial tissues from rats with mild and nonerosive arthritis, suggesting a vitamin D-mediated protective effect. In the present study, we address the hypothesis that part of the vitamin D protective effect is mediated via interference with fibroblast-like synoviocyte (FLS) invasive properties, an in vitro cellular phenotype that correlates with radiographic and histological damage in pristane-induced arthritis and RA. FLSs derived from DA rats with pristane-induced arthritis and RA patients were studied in an in vitro model of invasion through a collagen-rich barrier (Matrigel) over a 24-h period, in the presence or absence of calcitriol, an active form of vitamin D. Matrix metalloprotease (MMP) expression levels were analyzed with zymography and quantitative real-time polymerase chain reaction, and the cytoskeleton was studied with immunofluorescense microscopy. Calcitriol significantly inhibited DA and RA FLS invasion by 54% and 53%, respectively. Calcitriol also reduced interleukin (IL)-1β-induced expression of MMP-1 by 95% in DA FLSs and by 73.5% in RA FLS. Calcitriol treatment reduced actin cytoskeleton reorganization, reduced polarized formation of lamellipodia and reduced colocalization of phosphorylated focal adhesion kinase (p-FAK) with lamellipodia, all consistent with reduced cell ability to move and invade. In conclusion, we identified a new effect of calcitriol in FLS invasion. This discovery suggests that the reduced serum levels of vitamin D and its metabolites commonly seen in RA might increase risk for FLS-mediated cartilage and bone invasion and erosions. Treatment with vitamin D or its analogs has the potential to become a helpful adjuvant aimed at preventing or reducing joint destruction.



The authors wish to thank Cathleen Mason and Mary Keogh of the Feinstein Institute’s Tissue Donation Program for their assistance in obtaining the RA synovial tissues used in this study.

This study was funded by the National Institutes of Health, grants R01-AR46213, R01-AR052439 (NIAMS) and R01-AI54348 (NIAID), to PS Gulko.


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Authors and Affiliations

  • Teresina Laragione
    • 1
  • Anish Shah
    • 1
  • Pércio S. Gulko
    • 1
    • 2
  1. 1.Laboratory of Experimental Rheumatology, Center for Genomics and Human GeneticsFeinstein Institute for Medical ResearchManhassetUSA
  2. 2.Elmezzi Graduate School of Molecular MedicineManhassetUSA

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