Diabetes Activates Periodontal Ligament Fibroblasts via NF-κB In Vivo.

Area of Science:

• Oral Biology
• Endocrinology
• Immunology

Background:

• Diabetes mellitus is a known risk factor for periodontitis, increasing its severity and the pathogenicity of oral bacteria.
• The precise mechanisms by which diabetes influences periodontal tissues, particularly periodontal ligament (PDL) fibroblasts, remain incompletely understood.

Purpose of the Study:

• To investigate the impact of diabetes on PDL fibroblasts and their role in diabetes-associated periodontitis.
• To elucidate the molecular pathways, specifically nuclear factor kappa B (NF-κB) activation, involved in these changes.

Main Methods:

• Periodontitis was induced in normoglycemic and diabetic mice (streptozotocin-induced) via inoculation with Porphyromonas gingivalis and Fusobacterium nucleatum.
• In vivo studies utilized transgenic mice with lineage-specific NF-κB inhibition.
• In vitro experiments exposed PDL fibroblasts to high glucose conditions.

Main Results:

• Diabetes increased osteoclast numbers and neutrophil recruitment in the periodontal ligament, linked to elevated CXC motif chemokine 2 (CXCL2) and receptor activator of nuclear factor kappa B ligand (RANKL) expression.
• Diabetes significantly increased NF-κB expression and activation in PDL fibroblasts.
• PDL fibroblasts express an osteoblast-like regulatory element in their collagen type 1, alpha 1 (Col1α1) promoter.
• NF-κB inhibition in transgenic mice rescued diabetes-enhanced CXCL2 and RANKL expression.
• High glucose in vitro increased PDL fibroblast NF-κB activity, nuclear localization, and RANKL expression.

Conclusions:

• Diabetes induces alterations in PDL fibroblast gene expression via high glucose-induced NF-κB activation, promoting neutrophil recruitment and bone resorption.
• PDL fibroblasts possess an osteoblast-like regulatory element, suggesting a role in bone remodeling during periodontitis.
• Targeting NF-κB signaling in PDL fibroblasts may offer a therapeutic strategy for managing diabetes-associated periodontitis.