Strontium ion attenuates lipopolysaccharide-stimulated proinflammatory cytokine expression and lipopolysaccharide-inhibited early osteogenic differentiation of human periodontal ligament cells

J Periodontal Res. 2018 Dec;53(6):999-1008. doi: 10.1111/jre.12599. Epub 2018 Sep 17.

Abstract

Background and objective: Periodontitis is a chronic inflammatory disease characterized by the destruction of the periodontium. The strontium ion (Sr2+ ) can prevent the bone loss associated with periodontitis and promote the regeneration of the bone. The mechanisms by which the Sr2+ works remain poorly understood. We aim to investigate the effects of the Sr2+ ion on cell proliferation, inflammatory regulation and osteogenic differentiation of human periodontal ligament cells (hPDLCs) in pathological conditions.

Material and methods: hPDLCs were obtained from premolars that came from the orthodontic extraction. The hPDLCs were treated with Sr2+ and/or lipopolysaccharide (LPS), which was applied as the pathological condition of periodontitis. The effect of the dose of Sr2+ on cell proliferation was analyzed using a Cell Counting Kit-8 assay. The gene and protein expression of proinflammatory cytokines were detected by the real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The osteogenic differentiation and mineralization were assessed by the real-time polymerase chain reaction, alkaline phosphatase activity assay and alizarin red staining.

Results: Results demonstrated that Sr2+ in a range of concentrations from 0.02 to 2.5 mmol/L significantly improved the proliferation of hPDLCs. Sr2+ reversed LPS-stimulated proinflammatory cytokine expressions such as tumor necrosis factor alpha, interleukin (IL)-1β, IL-6 and IL-8. Moreover, Sr2+ rescued the LPS-inhibited gene expression of osteogenic differentiation. Although it appeared to suppress the late mineralization, Sr2+ can reverse the LPS-inhibited early osteogenic differentiation of hPDLCs.

Conclusion: These results indicated that Sr2+ could attenuate the LPS-stimulated proinflammatory molecule expression and inhibit early osteogenic differentiation of hPDLCs.

Keywords: human periodontal ligament cells; osteogenic differentiation; periodontitis; proinflammatory cytokines; strontium.

MeSH terms

  • Alveolar Bone Loss / etiology
  • Alveolar Bone Loss / pathology
  • Alveolar Bone Loss / prevention & control
  • Bone Regeneration / drug effects
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Chronic Periodontitis / complications
  • Chronic Periodontitis / pathology*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Inflammation Mediators / metabolism*
  • Lipopolysaccharides / adverse effects*
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology*
  • Periodontal Ligament / cytology*
  • Periodontal Ligament / metabolism*
  • Strontium / pharmacology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Strontium

Associated data

  • GENBANK/NM_001289745
  • GENBANK/XM_006710546
  • GENBANK/NM_001278478
  • GENBANK/NM_001251830
  • GENBANK/XM_005257058
  • GENBANK/NM_000594
  • GENBANK/XM_017003988
  • GENBANK/XM_005249745
  • GENBANK/NM_001354840