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HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption
Lin Chen1, Limin Liu2, Tianwei Lin1
1Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
International Dental Journal
|April 17, 2025
Summary
Epigenetic modification by HDAC9 promotes osteoclast differentiation and orthodontically induced inflammatory root resorption (OIIRR) by inducing mitochondrial dysfunction and pyroptosis. This study uncovers a key regulatory mechanism in OIIRR pathogenesis.
Area of Science:
- Biomedical research
- Molecular biology
- Dental science
Background:
- Orthodontically induced inflammatory root resorption (OIIRR) is a common complication of orthodontic treatment.
- Both epigenetic modifications and pyroptosis play roles in OIIRR, but their interaction is not fully understood.
Purpose of the Study:
- To investigate the role of epigenetic modifications in regulating pyroptosis during OIIRR.
- To elucidate the molecular mechanisms linking epigenetic changes to pyroptosis and subsequent OIIRR.
Main Methods:
- Established a rat model of OIIRR.
- Analyzed periodontal tissues using H&E staining, TRAP staining, immunofluorescence, transcriptome sequencing, and RT-qPCR.
- Utilized human periodontal ligament fibroblasts (hPDLFs) with HDAC9 overexpression, pyroptosis inhibition, and osteoclast co-incubation, followed by CUT&Tag sequencing.
Main Results:
- Transcriptome sequencing revealed upregulation of Hdac9 in OIIRR rat periodontal tissues.
- HDAC9 overexpression in hPDLFs induced pyroptosis, promoted osteoclast differentiation, and increased ROS levels.
- HDAC9-mediated deacetylation targeted mitochondrial dysfunction pathways, reducing H3K9ac enrichment on key genes.
Conclusions:
- HDAC9-mediated histone deacetylation drives mitochondrial dysfunction and pyroptosis in hPDLFs.
- This process promotes osteoclast differentiation and exacerbates OIIRR.
- The study provides novel insights into the epigenetic regulation of pyroptosis in OIIRR pathogenesis.

