1,25(OH)2D3and calcipotriol, its hypocalcemic analog, exert a long-lasting anti-inflammatory and anti-proliferative effect in synoviocytes cultured from patients with rheumatoid arthritis and osteoarthritis.
We 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).



Synovial stromal cells (SSC) isolated during knee prosthesis surgery from four patients with RA and four with OA were exposed to 1,25(OH)2D3or 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.



We 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)2D3and 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.



Exposure for 24-48h to 1,25(OH)2D3or calcipotriol causes a long-lasting inhibition of cell proliferation and cytokine production in SSC in vitro.
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Rheumatology Unit, Department of Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: johanna.huhtakangas@fimnet.fi.
Johanna A
JA
Huhtakangas
Biochemistry and Molecular Medicine Research Unit, Medical Research Center Oulu, Oulu University, Oulu, Finland. Electronic address: johanna.veijola@oulu.fi.
Johanna
J
Veijola
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: sanna.turunen@oulu.fi.
Sanna
S
Turunen
Rheumatology Unit, Department of Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: anna.karjalainen@ppshp.fi.
Anna
A
Karjalainen
Division of Operative Care, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: maarit.valkealahti@ppshp.fi.
Maarit
M
Valkealahti
Division of Operative Care, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: tomi.nousiainen@ppshp.fi.
Tomi
T
Nousiainen
Division of Operative Care, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: susanna.yli-luukko@ppshp.fi.
Susanna
S
Yli-Luukko
Biomedicine Unit, Department of Physiology, Medical Research Center Oulu, Oulu University, Oulu, Finland. Electronic address: olli.vuolteenaho@oulu.fi.
Olli
O
Vuolteenaho
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Division of Operative Care, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: petri.lehenkari@oulu.fi.
Petri
P
Lehenkari
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology; D000070918:Synoviocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; C055085:calcipotriene; D002117:Calcitriol
1,25(OH)(2)D(3); Apoptosis; Calcipotriol; Cytokines; Osteoarthritis; Rheumatoid arthritis; Synovial stromal cells