A vitronectin-derived peptide prevents and restores alveolar bone loss by modulating bone re-modelling and expression of RANKL and IL-17A

J Clin Periodontol. 2022 Aug;49(8):799-813. doi: 10.1111/jcpe.13671. Epub 2022 Jun 16.

Abstract

Aim: This study investigated whether a vitronectin-derived peptide (VnP-16) prevents and/or reverses alveolar bone resorption induced by ligature-induced periodontitis in rodents and identified the underlying mechanism.

Materials and methods: We evaluated the effects of VnP-16 on osteogenic differentiation in human periodontal ligament cells (hPDLCs), lipopolysaccharide-induced inflammatory responses in gingival fibroblasts, and immune response in T lymphocytes. Ligature-induced periodontitis was induced by ligating the bilateral mandibular first molars for 14 days in rats and for 7 days in mice (n = 10/group). VnP-16 (100 μg/10 μl) was applied topically into the gingival sulcus of rats via intra-sulcular injection, whereas the peptide (50 μg/5 μl) was administered directly into the gingiva of mice via intra-gingival injection. To evaluate the preventive and therapeutic effects of VnP-16, micro-computed tomography analysis and histological staining were then performed.

Results: VnP-16 promoted osteogenic differentiation of periodontal ligament cells and inhibited the production of lipopolysaccharide-induced inflammatory mediators in gingival fibroblasts. Concomitantly, VnP-16 modulated the host immune response by reducing the number of receptor activator of NF-κB ligand (RANKL)-expressing lipopolysaccharide-stimulated CD4+ and CD8+ T cells, and by suppressing RANKL and interleukin (IL)-17A production. Furthermore, local administration of VnP-16 in rats and mice significantly prevented and reversed alveolar bone loss induced by ligature-induced periodontitis. VnP-16 enhanced osteoblastogenesis and simultaneously inhibited osteoclastogenesis and suppressed RANKL and IL-17A expression in vivo.

Conclusions: Our findings suggest that VnP-16 acts as a potent therapeutic agent for preventing and treating periodontitis by regulating bone re-modelling and immune and inflammatory responses.

Keywords: alveolar bone loss; bone re-modelling; inflammatory responses; therapeutics; vitronectin-derived peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss* / drug therapy
  • Alveolar Bone Loss* / prevention & control
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Humans
  • Interleukin-17 / therapeutic use
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Mice
  • NF-kappa B
  • Osteogenesis
  • Periodontitis* / drug therapy
  • Periodontitis* / metabolism
  • Periodontitis* / prevention & control
  • RANK Ligand / metabolism
  • Rats
  • Vitronectin / therapeutic use
  • X-Ray Microtomography

Substances

  • IL17A protein, human
  • Il17a protein, mouse
  • Il17a protein, rat
  • Interleukin-17
  • Ligands
  • Lipopolysaccharides
  • NF-kappa B
  • RANK Ligand
  • TNFSF11 protein, human
  • Tnfsf11 protein, mouse
  • Vitronectin