Dental pulp stem cell-derived intracellular vesicles prevent orthodontic relapse by inhibiting PI3K/Akt/NF-κB-mediated osteoclast activity

Stem Cell Res Ther. 2025 Jan 23;16(1):22. doi: 10.1186/s13287-025-04146-3.

Abstract

Background: Orthodontic relapse, the undesired deviation of teeth from their corrected positions, remains a significant challenge in clinical orthodontics. Incomplete periodontal bone remodeling has been identified as a key factor in this process. Despite decades of research, currently there are no effective strategies to prevent relapse.

Methods: We isolated and identified dental pulp stem cell-derived intracellular vesicles (DPSC-IV) from human dental pulp tissue. To investigate its effect, DPSC-IV was added to osteoblast or osteoclast differentiation medium. During the orthodontic retention period, DPSC-IV was administrated to rats by subgingival injection. Relapse distance and relapse rate were calculated to evaluate DPSC-IV's ability to prevent relapse. Additionally, Western blot analysis were used to examine DPSC-IV's inhibitory effect on osteoclast differentiation.

Results: DPSC-IV significantly promoted osteoblast differentiation and inhibited osteoclast differentiation. Application of DPSC-IV during retention resulted in a significant reduction in both relapse distance and relapse rate, with improved periodontal structure and decreased osteoclast activity. This effect was mediated by the PI3K/Akt/NF-κB signaling pathway and could be reversed by the PI3K activator insulin-like growth factor-1 (IGF-1).

Conclusion: This study highlights the potential of DPSC-IV as a novel preventive approach against orthodontic relapse, offering a novel strategy for maintaining long-term orthodontic stability.

Keywords: Bone remodeling; Cell communication; Intercellular vesicles; Oral medicine; Orthodontic tooth movement; Stem cells.

MeSH terms

  • Adolescent
  • Animals
  • Cell Differentiation* / drug effects
  • Dental Pulp* / cytology
  • Dental Pulp* / metabolism
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Male
  • NF-kappa B* / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoclasts* / cytology
  • Osteoclasts* / drug effects
  • Osteoclasts* / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Stem Cells* / cytology
  • Stem Cells* / metabolism

Substances

  • NF-kappa B
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Insulin-Like Growth Factor I