Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis
Introduction: Periodontitis is the sixth most common human disease and epigenetic regulation is identified to affect the functions of stem cells. This research aims to analyze the role of histone demethylase Lysine-specific demethylase 5A (KDM5A) in human periodontal ligament stem cells (hPDLSCs) wi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320421000997 |
| _version_ | 1811231382843686912 |
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| author | Fang Niu Jing Xu Yujuan Yan |
| author_facet | Fang Niu Jing Xu Yujuan Yan |
| author_sort | Fang Niu |
| collection | DOAJ |
| description | Introduction: Periodontitis is the sixth most common human disease and epigenetic regulation is identified to affect the functions of stem cells. This research aims to analyze the role of histone demethylase Lysine-specific demethylase 5A (KDM5A) in human periodontal ligament stem cells (hPDLSCs) with periodontitis. Methods: hPDLSCs were treated with porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) and subjected to osteogenic induction. The expression of KDM5A was detected by RT-qPCR and Western blot. Then, KDM5A expression patterns in hPDLSCs were measured and then silenced using shRNA to explore its role in osteogenic differentiation (OD), proliferation, and migration of hPDLSCs. ChIP assay was used to analyze the relationship between KDM5A and miR-495-3p, Western blot was used to detect H3K4me3 and RT-qPCR was used to detect miR-495-3p expression. CPI-455 (specific KDM5 inhibitor) was adopted to confirm the role of H3K4me3, and dual-Luciferase assay indicted the relationship between miR-495-3p and homeobox C8 (HOXC8). A functional rescue experiment was designed to analyze the role of miR-495-3p in hPDLSCs with periodontitis. Results: KDM5A was highly expressed in LPS-treated hPDLSCs. Downregulation of KDM5A promoted OD, proliferation, and migration of hPDLSCs. Mechanically, KDM5A inhibited miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription. Downregulation of miR-495-3p could weaken the effect of sh-KDM5A to promote OD, proliferation, and migration of hPDLSCs. Conclusions: KDM5A could bind to the miR-495-3p promoter and inhibit miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription, thereby increasing the HOXC8 and limiting OD, proliferation, and migration of hPDLSCs with periodontitis. |
| first_indexed | 2024-04-12T10:44:21Z |
| format | Article |
| id | doaj.art-1d293448bb3945768b552133bb968c28 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-12T10:44:21Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-1d293448bb3945768b552133bb968c282022-12-22T03:36:29ZengElsevierRegenerative Therapy2352-32042022-06-012095106Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axisFang Niu0Jing Xu1Yujuan Yan2Department of Oral Implantology and Prosthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, PR China; Corresponding author. Department of Oral Implantology and Prosthodontics, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou, Henan Province, 450000, China.Department of Oral Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, PR ChinaDepartment of Oral Prosthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, PR ChinaIntroduction: Periodontitis is the sixth most common human disease and epigenetic regulation is identified to affect the functions of stem cells. This research aims to analyze the role of histone demethylase Lysine-specific demethylase 5A (KDM5A) in human periodontal ligament stem cells (hPDLSCs) with periodontitis. Methods: hPDLSCs were treated with porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) and subjected to osteogenic induction. The expression of KDM5A was detected by RT-qPCR and Western blot. Then, KDM5A expression patterns in hPDLSCs were measured and then silenced using shRNA to explore its role in osteogenic differentiation (OD), proliferation, and migration of hPDLSCs. ChIP assay was used to analyze the relationship between KDM5A and miR-495-3p, Western blot was used to detect H3K4me3 and RT-qPCR was used to detect miR-495-3p expression. CPI-455 (specific KDM5 inhibitor) was adopted to confirm the role of H3K4me3, and dual-Luciferase assay indicted the relationship between miR-495-3p and homeobox C8 (HOXC8). A functional rescue experiment was designed to analyze the role of miR-495-3p in hPDLSCs with periodontitis. Results: KDM5A was highly expressed in LPS-treated hPDLSCs. Downregulation of KDM5A promoted OD, proliferation, and migration of hPDLSCs. Mechanically, KDM5A inhibited miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription. Downregulation of miR-495-3p could weaken the effect of sh-KDM5A to promote OD, proliferation, and migration of hPDLSCs. Conclusions: KDM5A could bind to the miR-495-3p promoter and inhibit miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription, thereby increasing the HOXC8 and limiting OD, proliferation, and migration of hPDLSCs with periodontitis.http://www.sciencedirect.com/science/article/pii/S2352320421000997PeriodontitishPDLSCsHistone demethylaseKDM5AmiR-495-3pStem cell function |
| spellingShingle | Fang Niu Jing Xu Yujuan Yan Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis Regenerative Therapy Periodontitis hPDLSCs Histone demethylase KDM5A miR-495-3p Stem cell function |
| title | Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis |
| title_full | Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis |
| title_fullStr | Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis |
| title_full_unstemmed | Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis |
| title_short | Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis |
| title_sort | histone demethylase kdm5a regulates the functions of human periodontal ligament stem cells during periodontitis via the mir 495 3p hoxc8 axis |
| topic | Periodontitis hPDLSCs Histone demethylase KDM5A miR-495-3p Stem cell function |
| url | http://www.sciencedirect.com/science/article/pii/S2352320421000997 |
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