1,25(OH)2D3 and calcipotriol, its hypocalcemic analog, exert a long-lasting anti-inflammatory and anti-proliferative effect in synoviocytes cultured from patients with rheumatoid arthritis and osteoarthritis

- Inflammatory cytokines secreted by synovial stromal cells of patients with rheumatoid arthritis or osteoarthritis may play a role in disease pathogenesis.
- 1,25(OH)2D3 and calcipotriol, its hypocalcemic analog, are strong negative regulators of cell proliferation and cytokine secretion in synovial stromal cells.
- This in-vitro study suggests a potential advantageous effect of calcipotriol in treatment of arthritis, but it should be further addressed in a separate in vivo study.

ObjectivesWe investigated the effects of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3), i.e. biologically active vitamin D and calcipotriol, a vitamin D analog, on growth and secretion of inflammatory mediators in synovial stromal cells (SSC) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA).MethodsSynovial stromal cells (SSC) isolated during knee prosthesis surgery from four patients with RA and four with OA were exposed to 1,25(OH)2D3 or calcipotriol with or without stimulation of cells with IL-1β or TNF-α. The proliferation of cells was studied by MTT assay. Levels of cytokines were analyzed by a magnetic bead-based multiplex assay (a panel of 27 important cytokines and IL-6 alone) and RT-PCR was used to validate the concentrations of the key cytokines secreted by SSC. The vitamin D receptor (VDR) was visualized by immunofluorescence in SSC and by immunohistochemistry in the synovial tissues of three RA and three OA patients.ResultsWe detected intense staining for VDR in the synovial lining and vascular endothelium in tissue sections from all our RA and OA patients. Both 1,25(OH)2D3 and calcipotriol inhibited SSC proliferation for a prolonged time (up to 23 days with calcipotriol), but dexamethasone tended to increase SSC proliferation in a 4-day culture. 1,25(OH)2D3, calcipotriol and dexamethasone reduced the secretion of most inflammatory factors. Calcipotriol and dexamethasone additively reduced the secretions of IL-6, IFN-γ, basic FGF and VEGF in TNF-α stimulated SSC. The level of IL-6 was still diminished at 10 days after exposure, emphasizing the long-term impact of calcipotriol on SSC.ConclusionsExposure for 24-48 h to 1,25(OH)2D3 or calcipotriol causes a long-lasting inhibition of cell proliferation and cytokine production in SSC in vitro.