Notch signalling cascade and proinflammatory mediators in peri-implant lesions with different RANKL/OPG ratios-An observational study

J Periodontal Res. 2023 Apr;58(2):360-368. doi: 10.1111/jre.13096. Epub 2023 Jan 8.

Abstract

Background & objective: Notch signaling pathway has been linked to bone loss in periodontitis and peri-implantitis. This research aimed to determine the Notch signaling molecules expression levels (Notch1, Notch2, Jagged1, Hes1, and Hey1), along with bone remodeling mediators (RANKL and OPG) and proinflammatory cytokines (TNF-α, IL-17, IL-1β, and IL-6) in patients with peri-implant diseases. The aforementioned markers' expression was evaluated in patients with different RANKL/OPG ratios.

Methods: Fifty patients with peri-implantitis (PI group) and 45 patients with peri-implant mucositis (PM group) were enrolled. Relative gene expression levels of investigated molecules were determined by reverse transcriptase-real-time polymerase chain reaction. On the basis of RANKL/OPG ratio, all peri-implant lesions were divided into subgroups: RANKL-predominant (RANKL > OPG) and OPG-predominant (RANKL < OPG). Clinical periodontal parameters (probing depth-PD, bleeding on probing-BOP, clinical attachment level-CAL and plaque index-PLI), were recorded for each patient around every tooth, and around placed implants (PDi, BOPi, CALi, PLIi).

Results: RANKL-predominant PM patients exhibited higher expression levels of Notch2 (p = .044) and Hey1 (p = .005) compared to OPG-predominant lesions. In all RANKL-predominant cases, Hey1 (p = .001), IL-1β (p = .005), IL-6 (p = .002) were overexpressed in PI comparing to PM, accompanied with significantly higher PDi, CALi and PLIi in PI than PM (p = .001, p = .001 and p = .009).

Conclusions: Notch2 upregulation in RANKL-predominant PM lesions could be an important contributor to alveolar bone resorption and represent a predictor of PM to PI transition. Similarly, the overexpression of IL-1β and IL-6 might provide an osteoclastogenic environment in PI RANKL-predominant lesions.

Keywords: Notch signaling; gene expression; peri-implant mucositis; peri-implantitis.

Publication types

  • Observational Study

MeSH terms

  • Alveolar Bone Loss* / metabolism
  • Alveolar Bone Loss* / pathology
  • Cytokines / metabolism
  • Dental Implants / adverse effects
  • Humans
  • Interleukin-6
  • Osteoprotegerin / metabolism
  • Peri-Implantitis* / metabolism
  • RANK Ligand / metabolism
  • Receptors, Notch* / metabolism
  • Signal Transduction*

Substances

  • Cytokines
  • Dental Implants
  • Interleukin-6
  • Receptors, Notch
  • RANK Ligand
  • TNFRSF11B protein, human
  • Osteoprotegerin