Fibroblast growth factor-2 inhibits CD40-mediated periodontal inflammation

J Cell Physiol. 2019 May;234(5):7149-7160. doi: 10.1002/jcp.27469. Epub 2018 Oct 28.

Abstract

Fibroblast growth factor-2 (FGF-2) stimulates periodontal regeneration by a broad spectrum of effects on periodontal ligament (PDL) cells, such as proliferation, migration, and production of extracellular matrix. A critical factor in the success of periodontal regeneration is the rapid resolution of inflammatory responses in the tissue. We explored an anti-inflammatory effect of FGF-2 during periodontal regeneration and healing. We found that FGF-2 on mouse periodontal ligament cells (MPDL22) markedly downregulated CD40 expression, a key player of inflammation. In addition, FGF-2 inhibited CD40 signaling by the non-canonical nuclear factor-kappa B2 (NFκB2) pathway, resulting in decreased production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which have the potential to recruit immune cells to inflamed sites. Furthermore, in vivo treatment of FGF-2 enhanced healing of skin wounds by counteracting the CD40-mediated inflammation. These results reveal that FGF-2 has an important function as a negative regulator of inflammation during periodontal regeneration and healing.

Keywords: CD40; anti-inflammation; fibroblast growth factor-2 (FGF-2); periodontal ligament (PDL) cells; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism*
  • Cell Line
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / pharmacology*
  • Interleukin-6 / metabolism
  • Male
  • Mice, Inbred BALB C
  • NF-kappa B p52 Subunit / metabolism
  • Periodontal Ligament / drug effects*
  • Periodontal Ligament / metabolism
  • Periodontal Ligament / pathology
  • Periodontitis / genetics
  • Periodontitis / metabolism
  • Periodontitis / pathology
  • Periodontitis / prevention & control*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing / drug effects
  • Wounds, Penetrating / drug therapy
  • Wounds, Penetrating / metabolism
  • Wounds, Penetrating / pathology

Substances

  • Anti-Inflammatory Agents
  • CD40 Antigens
  • Interleukin-6
  • NF-kappa B p52 Subunit
  • Nfkb2 protein, mouse
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Fibroblast Growth Factor 2