Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs)

Cell Physiol Biochem. 2017;41(5):1725-1735. doi: 10.1159/000471865. Epub 2017 Mar 31.

Abstract

Background/aims: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs).

Methods: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment.

Results: Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo.

Conclusion: TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.

Keywords: BMP9; Bone regeneration; Dental regeneration; Inflammation; Mesenchymal stem cells; Osteogenesis; Periapical periodontitis; TNF-α.

Publication types

  • Retracted Publication

MeSH terms

  • Alkaline Phosphatase / biosynthesis
  • Animals
  • Cell Differentiation*
  • Enzyme Induction
  • Growth Differentiation Factor 2 / metabolism*
  • Male
  • Odontoblasts / metabolism*
  • Odontoblasts / pathology
  • Periapical Periodontitis / metabolism*
  • Periapical Periodontitis / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Growth Differentiation Factor 2
  • Tumor Necrosis Factor-alpha
  • Alkaline Phosphatase