Integrated bioinformatic analysis of protein landscape in gingival crevicular fluid unveils sequential bioprocess in orthodontic tooth movement

Prog Orthod. 2024 Sep 23;25(1):37. doi: 10.1186/s40510-024-00536-0.

Abstract

Background: The biological mechanisms driving orthodontic tooth movement (OTM) remain incompletely understood. Gingival crevicular fluid (GCF) is an important indicator of the periodontal bioprocess, providing valuable cues for probing the molecular mechanisms of OTM.

Methods: A rigorous review of the clinical studies over the past decade was conducted after registering the protocol with PROSPERO and adhering to inclusion criteria comprising human subjects, specified force magnitudes and force application modes. The thorough screening investigated differentially expressed proteins (DEPs) in GCF associated with OTM. Protein-protein interaction (PPI) analysis was carried out using the STRING database, followed by further refinement through Cytoscape to isolate top hub proteins.

Results: A comprehensive summarization of the OTM-related GCF studies was conducted, followed by an in-depth exploration of biomarkers within the GCF. We identified 13 DEPs, including ALP, IL-1β, IL-6, Leptin, MMP-1, MMP-3, MMP-8, MMP-9, PGE2, TGF-β1, TNF-α, OPG, RANKL. Bioinformatic analysis spotlighted the top 10 hub proteins and their interactions involved in OTM. Based on these findings, we have proposed a hypothetic diagram for the time-course bioprocess in OTM, which involves three phases containing sequential cellular and molecular components and their interplay network.

Conclusions: This work has further improved our understanding to the bioprocess of OTM, suggesting biomarkers as potential modulating targets to enhance OTM, mitigate adverse effects and support real-time monitoring and personalized orthodontic cycles.

Keywords: Bioinformatic analysis; Biomarker; Cytokine; Gingival crevicular fluid; Orthodontic tooth movement.

Publication types

  • Review

MeSH terms

  • Biomarkers* / analysis
  • Computational Biology* / methods
  • Dinoprostone / analysis
  • Dinoprostone / metabolism
  • Gingival Crevicular Fluid* / chemistry
  • Gingival Crevicular Fluid* / metabolism
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Leptin / analysis
  • Leptin / metabolism
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 3 / analysis
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 8 / analysis
  • Matrix Metalloproteinase 8 / metabolism
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / metabolism
  • Osteoprotegerin / analysis
  • Osteoprotegerin / metabolism
  • Protein Interaction Maps
  • RANK Ligand / analysis
  • RANK Ligand / metabolism
  • Tooth Movement Techniques* / methods
  • Transforming Growth Factor beta1 / analysis
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • RANK Ligand
  • Osteoprotegerin
  • Tumor Necrosis Factor-alpha
  • Transforming Growth Factor beta1
  • Leptin
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 8
  • Interleukin-6
  • MMP3 protein, human
  • TNFSF11 protein, human
  • Matrix Metalloproteinase 9
  • Dinoprostone
  • Matrix Metalloproteinase 1
  • TNFRSF11B protein, human