KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression
Objective: Periodontal ligament stem cells (PDLSCs) are emerging as a promising source for periodontal regeneration and to manage periodontitis. This study aims to investigate the roles of Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-related factor (Nrf2) in mediating osteogenic diffe...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | International Dental Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0020653925000607 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850279279650144256 |
|---|---|
| author | Jiujiu Chen Lichao Deng |
| author_facet | Jiujiu Chen Lichao Deng |
| author_sort | Jiujiu Chen |
| collection | DOAJ |
| description | Objective: Periodontal ligament stem cells (PDLSCs) are emerging as a promising source for periodontal regeneration and to manage periodontitis. This study aims to investigate the roles of Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-related factor (Nrf2) in mediating osteogenic differentiation of human PDLSCs (hPDLSCs) in the context of lipopolysaccharide (LPS) stimulation. Methods: The osteogenic differentiation potential of hPDLSCs isolated from human premolar root samples were examined by alkaline phosphatase (ALP) staining and ALP activity assay, Alizarin red S staining and quantitative analysis of mineralised matrix. Intracellular reactive oxygen species (ROS) production and glutathione (GSH) concentration were assessed to reflect oxidative stress. Results: KLF2 overexpression influenced Nrf2-regulated transcription, leading to significant increases in GSH concentration, ALP activity, mineralised matrix formation, and RUNX2 expression in LPS-stimulated hPDLSCs, as well as significant reductions in ROS production and cell apoptosis. The subsequent Nrf2 knockdown impaired the protective effect of KLF2 on hPDLSCs against LPS stimulation. Conclusion: The findings of the study demonstrate KLF2 overexpression has the ability to promote the osteogenic differentiation of hPDLSCs by promoting Nrf2 activation, suggesting that KLF2 mediating Nrf2 could be a promising target to facilitate the efficacy of PDLSC-based bone regeneration in periodontitis. |
| format | Article |
| id | doaj-art-1bd7a71944274a68872bdfd96ecf4992 |
| institution | OA Journals |
| issn | 0020-6539 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Dental Journal |
| spelling | doaj-art-1bd7a71944274a68872bdfd96ecf49922025-08-20T01:49:08ZengElsevierInternational Dental Journal0020-65392025-06-017531554156310.1016/j.identj.2025.02.019KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 ExpressionJiujiu Chen0Lichao Deng1Pediatric Dentistry, Wenzhou Dental Hospital, Wenzhou, Zhejiang, ChinaEndodontic Department, School & Hospital of Stomatology Wenzhou Medical University, Wenzhou, Zhejiang, China; Corresponding author. Endodontic Department, School & Hospital of Stomatology Wenzhou Medical University, No. 1288 Longyao Avenue, Longwan District, Wenzhou, Zhejiang 325000, China.Objective: Periodontal ligament stem cells (PDLSCs) are emerging as a promising source for periodontal regeneration and to manage periodontitis. This study aims to investigate the roles of Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-related factor (Nrf2) in mediating osteogenic differentiation of human PDLSCs (hPDLSCs) in the context of lipopolysaccharide (LPS) stimulation. Methods: The osteogenic differentiation potential of hPDLSCs isolated from human premolar root samples were examined by alkaline phosphatase (ALP) staining and ALP activity assay, Alizarin red S staining and quantitative analysis of mineralised matrix. Intracellular reactive oxygen species (ROS) production and glutathione (GSH) concentration were assessed to reflect oxidative stress. Results: KLF2 overexpression influenced Nrf2-regulated transcription, leading to significant increases in GSH concentration, ALP activity, mineralised matrix formation, and RUNX2 expression in LPS-stimulated hPDLSCs, as well as significant reductions in ROS production and cell apoptosis. The subsequent Nrf2 knockdown impaired the protective effect of KLF2 on hPDLSCs against LPS stimulation. Conclusion: The findings of the study demonstrate KLF2 overexpression has the ability to promote the osteogenic differentiation of hPDLSCs by promoting Nrf2 activation, suggesting that KLF2 mediating Nrf2 could be a promising target to facilitate the efficacy of PDLSC-based bone regeneration in periodontitis.http://www.sciencedirect.com/science/article/pii/S0020653925000607Periodontitistissue engineeringregenerationinflammation |
| spellingShingle | Jiujiu Chen Lichao Deng KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression International Dental Journal Periodontitis tissue engineering regeneration inflammation |
| title | KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression |
| title_full | KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression |
| title_fullStr | KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression |
| title_full_unstemmed | KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression |
| title_short | KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression |
| title_sort | klf2 promotes osteogenic differentiation of human periodontal ligament stem cells by regulating nrf2 expression |
| topic | Periodontitis tissue engineering regeneration inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0020653925000607 |
| work_keys_str_mv | AT jiujiuchen klf2promotesosteogenicdifferentiationofhumanperiodontalligamentstemcellsbyregulatingnrf2expression AT lichaodeng klf2promotesosteogenicdifferentiationofhumanperiodontalligamentstemcellsbyregulatingnrf2expression |