1α,25‐dihydroxyvitaminD3 promotes osteogenic activity and downregulates proinflammatory cytokine expression in human periodontal ligament cells

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Abstract
Background and Objective: The aim of this study was to assess the impact of 1α,25‐dihydroxyvitamin D3 (vitamin D3) on osteogenic and inflammatory properties of human periodontal ligament (PDL) cells and investigate underlying mechanisms.Material and Methods: HumanPDLcells, obtained from four subjects, were stimulated with vitaminD3 for 4–48 h. The bone markers osteopontin and osteocalcin and proinflammatory cytokine/chemokine expression was determined by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Cytokine and chemokine expression was determined after stimulation with the inflammation promoter lipopolysaccharide (LPS) in the presence or absence of vitaminD3. Alkaline phosphatase activity was assessed usingp‐nitrophenylphosphate substrate.Results: Treatment with 30 ng/mLof vitamin D3, corresponding to an optimal plasma concentration of vitaminD, for 24 h had no effect onPDLcell number and morphology but increased PDL cell osteopontin and osteocalcin mRNAexpression by about 70 and 40%, respectively, and, moreover, treatment with vitaminD3 for 48 h enhancedPDLcell alkaline phosphatase activity by about two times showing that vitaminD3 exerts pro‐osteogenic effects in humanPDLcells. Stimulation withLPS(1 μg/mL) for 4 h increasedPDLcell interleukin (IL)‐6 cytokine and chemokine ligand 1 (CXCL1) chemokine mRNAexpression several fold. TheLPS‐induced increase inIL‐6 andCXCL1 transcripts was attenuated by vitaminD3 (30 ng/mL). Treatment with vitaminD3 (3–300 ng/mL) for 24 h reduced theLPS‐evoked increase inPDLcellIL‐6 protein by about 50%. VitaminD3 (30 ng/mL) had no effect onLPS‐inducedIL‐1β andMCP‐1 mRNAexpression.Conclusions: VitaminD3 promotes osteogenic differentiation but also downregulates inflammation promoter‐inducedIL‐6 cytokine andCXCL1 chemokine expression in humanPDLcells, suggesting that vitaminD3 both stimulates bone regeneration and antagonizes inflammation in human periodontal tissue.
Funding Information
  • Swedish Research Council
  • Faculty of Odontology at Malmö University
  • Medical Faculty at Lund University
  • Swedish Dental Society
  • Foundations of Crafoord, Lars Hierta, Sven and Lilly Thuréus and Greta and Johan Kock

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