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Updated: May 28, 2026

In situ Compressive Loading and Correlative Noninvasive Imaging of the Bone-periodontal Ligament-tooth Fibrous Joint
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Published on: March 7, 2014

HELLS Reduction Contributes to Compressive Force-Induced Functional Changes in PDLSCs.

Manqi Wang1,2,3, Qian Li1,2,3, Jiaqi Chen1,2,3

  • 1National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.

International Journal of Molecular Sciences
|May 27, 2026
PubMed
Summary
This summary is machine-generated.

Mechanical forces during orthodontic tooth movement (OTM) reduce the epigenetic regulator HELLS in periodontal ligament stem cells (PDLSCs). This downregulation impairs bone formation and promotes bone resorption, influencing OTM.

Keywords:
HELLScompressive forceorthodontic tooth movementosteogenic differentiationperiodontal ligament stem cells

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Area of Science:

  • Biomedical Engineering
  • Stem Cell Biology
  • Epigenetics

Background:

  • Orthodontic tooth movement (OTM) relies on bone remodeling, but the cellular sensing of mechanical forces is unclear.
  • Periodontal ligament stem cells (PDLSCs) are key players in this process, responding to mechanical stimuli.

Purpose of the Study:

  • To identify molecular mechanisms in human PDLSCs (hPDLSCs) responding to mechanical forces.
  • To investigate the role of the epigenetic regulator HELLS as a mechanosensitive mediator in hPDLSCs during OTM.

Main Methods:

  • Compressive force applied to hPDLSCs in vitro and in a mouse OTM model.
  • HELLS expression analyzed via qPCR and Western blotting.
  • Functional assays including Alizarin Red S staining and alkaline phosphatase activity.
  • siRNA-mediated HELLS knockdown to assess effects on differentiation and gene expression.
  • Transcriptomic analysis to identify affected pathways.
  • Co-culture assays with RAW264.7 cells to evaluate osteoclastogenesis.
  • E2F1 identified as a potential transcription factor.

Main Results:

  • Compressive force significantly downregulated HELLS expression in hPDLSCs.
  • HELLS knockdown impaired osteogenic differentiation and altered mechanotransduction pathways.
  • HELLS deficiency increased YAP and RANKL expression.
  • Osteoclast differentiation was enhanced in co-cultured cells upon HELLS knockdown.
  • E2F1 was identified as a transcription factor involved in HELLS regulation.

Conclusions:

  • HELLS acts as a mechano-epigenetic regulator in hPDLSCs.
  • Force-induced HELLS downregulation contributes to alveolar bone remodeling during OTM.
  • This downregulation influences OTM by reducing osteogenesis and increasing pro-osteoclastogenic signaling.