HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption
Introduction and aims: Orthodontically induced inflammatory root resorption (OIIRR) is a common iatrogenic outcome of orthodontic treatment. Both epigenetic modifications and pyroptosis have demonstrated a certain role in OIIRR. This study aims to investigate whether epigenetic modifications regulat...
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| Format: | Article |
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Elsevier
2025-06-01
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| Series: | International Dental Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S002065392500098X |
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| author | Lin Chen Limin Liu Tianwei Lin Zhihui Mai Hongfei Lu Bingxue Hu Junhao Huang Hong Ai |
| author_facet | Lin Chen Limin Liu Tianwei Lin Zhihui Mai Hongfei Lu Bingxue Hu Junhao Huang Hong Ai |
| author_sort | Lin Chen |
| collection | DOAJ |
| description | Introduction and aims: Orthodontically induced inflammatory root resorption (OIIRR) is a common iatrogenic outcome of orthodontic treatment. Both epigenetic modifications and pyroptosis have demonstrated a certain role in OIIRR. This study aims to investigate whether epigenetic modifications regulate pyroptosis to be involved in OIIRR. Method: Rat model of OIIRR was established, and the periodontal tissues were utilized for H&E staining, TRAP staining, immunofluorescence, transcriptome sequencing, and RT-qPCR analysis. Human periodontal ligament fibroblasts (hPDLFs) were overexpressed with HDAC9, treated with pyroptosis inhibitor, incubated with osteoclast, and then subjected to CUT&Tag sequencing. Results: Orthodontic force increased the distance of orthodontic tooth movement and the abundance of osteoclast. Transcriptome sequencing identified that Hdac9 was upregulated in the periodontal tissues of OIIRR rats compared to the control. Immunofluorescence revealed that HDAC9 was present in periodontal ligament fibroblasts, with reduced fluorescence of HDAC9 in OIIRR compared to the control. HDAC9 overexpression in hPDLFs induced pyroptosis and promoted osteoclast differentiation. These effects were reversed by pyroptosis inhibitor. CUT&Tag analysis showed that HDAC9 overexpression resulted in an enrichment of deacetylated genes on mitochondrial dysfunction-associated pathways. CUT&Tag-PCR analysis confirmed reduced H3K9ac enrichment on the mitochondrial dysfunction-associated genes VPS13D, AQP1, PEX2, CDK1, and PLEKHA1 after HDAC9 overexpression, and RT-qPCR analysis revealed a corresponding decrease in their respective expression levels. Accordingly, the ROS level was also increased by HDAC9 overexpression. Conclusion: HDAC9-mediated histone deacetylation induces mitochondrial dysfunction and pyroptosis in hPDLFs, thereby promoting osteoclast differentiation and OIIRR progression. Clinical relevance: This study reveals the regulatory mechanism of pyroptosis in OIIRR from the perspective of epigenetic modifications, providing new insights into the pathogenesis of OIIRR. |
| format | Article |
| id | doaj-art-68e564e4dc5b4b1e9ff7ead65b438e37 |
| institution | DOAJ |
| issn | 0020-6539 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Dental Journal |
| spelling | doaj-art-68e564e4dc5b4b1e9ff7ead65b438e372025-08-20T03:09:11ZengElsevierInternational Dental Journal0020-65392025-06-017531828184210.1016/j.identj.2025.03.018HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root ResorptionLin Chen0Limin Liu1Tianwei Lin2Zhihui Mai3Hongfei Lu4Bingxue Hu5Junhao Huang6Hong Ai7Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaHospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Corresponding author. Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tian He Road, Tianhe District, Guangzhou 510000, China.Introduction and aims: Orthodontically induced inflammatory root resorption (OIIRR) is a common iatrogenic outcome of orthodontic treatment. Both epigenetic modifications and pyroptosis have demonstrated a certain role in OIIRR. This study aims to investigate whether epigenetic modifications regulate pyroptosis to be involved in OIIRR. Method: Rat model of OIIRR was established, and the periodontal tissues were utilized for H&E staining, TRAP staining, immunofluorescence, transcriptome sequencing, and RT-qPCR analysis. Human periodontal ligament fibroblasts (hPDLFs) were overexpressed with HDAC9, treated with pyroptosis inhibitor, incubated with osteoclast, and then subjected to CUT&Tag sequencing. Results: Orthodontic force increased the distance of orthodontic tooth movement and the abundance of osteoclast. Transcriptome sequencing identified that Hdac9 was upregulated in the periodontal tissues of OIIRR rats compared to the control. Immunofluorescence revealed that HDAC9 was present in periodontal ligament fibroblasts, with reduced fluorescence of HDAC9 in OIIRR compared to the control. HDAC9 overexpression in hPDLFs induced pyroptosis and promoted osteoclast differentiation. These effects were reversed by pyroptosis inhibitor. CUT&Tag analysis showed that HDAC9 overexpression resulted in an enrichment of deacetylated genes on mitochondrial dysfunction-associated pathways. CUT&Tag-PCR analysis confirmed reduced H3K9ac enrichment on the mitochondrial dysfunction-associated genes VPS13D, AQP1, PEX2, CDK1, and PLEKHA1 after HDAC9 overexpression, and RT-qPCR analysis revealed a corresponding decrease in their respective expression levels. Accordingly, the ROS level was also increased by HDAC9 overexpression. Conclusion: HDAC9-mediated histone deacetylation induces mitochondrial dysfunction and pyroptosis in hPDLFs, thereby promoting osteoclast differentiation and OIIRR progression. Clinical relevance: This study reveals the regulatory mechanism of pyroptosis in OIIRR from the perspective of epigenetic modifications, providing new insights into the pathogenesis of OIIRR.http://www.sciencedirect.com/science/article/pii/S002065392500098XHDAC9PyroptosisPeriodontal ligament fibroblastsOrthodontically induced inflammatory root resorptionMitochondrial dysfunction |
| spellingShingle | Lin Chen Limin Liu Tianwei Lin Zhihui Mai Hongfei Lu Bingxue Hu Junhao Huang Hong Ai HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption International Dental Journal HDAC9 Pyroptosis Periodontal ligament fibroblasts Orthodontically induced inflammatory root resorption Mitochondrial dysfunction |
| title | HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption |
| title_full | HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption |
| title_fullStr | HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption |
| title_full_unstemmed | HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption |
| title_short | HDAC9-Mediated Pyroptosis Promotes Orthodontically Induced Inflammatory Root Resorption |
| title_sort | hdac9 mediated pyroptosis promotes orthodontically induced inflammatory root resorption |
| topic | HDAC9 Pyroptosis Periodontal ligament fibroblasts Orthodontically induced inflammatory root resorption Mitochondrial dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S002065392500098X |
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