CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth
Dental caries, a prevalent global health issue, results from complex bacterial interactions. In response to harmful stimuli, a desirable outcome for the tooth is the formation of tertiary dentin, a protective reparative process that generates new hard tissue. This reparative dentinogenesis is associ...
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| Format: | Article |
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eLife Sciences Publications Ltd
2025-07-01
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| Online Access: | https://elifesciences.org/articles/105153 |
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| author | Ji Hyun Kim Muhammad Irfan Sreelekshmi Sreekumar Atsawasuwan Phimon Stephanie Kim Seung Chung |
| author_facet | Ji Hyun Kim Muhammad Irfan Sreelekshmi Sreekumar Atsawasuwan Phimon Stephanie Kim Seung Chung |
| author_sort | Ji Hyun Kim |
| collection | DOAJ |
| description | Dental caries, a prevalent global health issue, results from complex bacterial interactions. In response to harmful stimuli, a desirable outcome for the tooth is the formation of tertiary dentin, a protective reparative process that generates new hard tissue. This reparative dentinogenesis is associated with significant inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs). Previously, we have demonstrated that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB), key mediators of neural functions, are activated during the DPSC-mediated dentin regeneration process. In this study, we further define the role of inflammation in this process and apply stem cell engineering to enhance dentin regeneration in injured teeth. Our data show that TrkB expression and activation in DPSCs rapidly increase during odontogenic differentiation, further amplified by inflammatory inducers and mediators such as tumor necrosis factor alpha (TNFα), lymphotoxin-alpha, and lipopolysaccharide. An in vivo dentin formation assessment was conducted using a mouse pulp-capping/caries model, where Clustered Regularly Interspaced Short Palindromic Repeats-engineered DPSCs overexpressing BDNF were transplanted into inflamed pulp tissue. This transplantation significantly enhanced dentin regeneration in injured teeth. To further explore potential downstream pathways, we conducted transcriptomic profiling of TNFα-treated DPSCs, both with and without TrkB antagonist cyclotraxin-B. The results revealed significant changes in gene expression related to immune response, cytokine signaling, and extracellular matrix interactions. Taken together, our study advances our understanding of the role of BDNF in dental tissue engineering using DPSCs and identifies potential therapeutic avenues for improving dental tissue repair and regeneration strategies. |
| format | Article |
| id | doaj-art-0950be609728409fbacbb0a4185b2c2a |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-0950be609728409fbacbb0a4185b2c2a2025-08-20T03:50:06ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011410.7554/eLife.105153CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teethJi Hyun Kim0Muhammad Irfan1https://orcid.org/0000-0002-9788-8231Sreelekshmi Sreekumar2Atsawasuwan Phimon3Stephanie Kim4Seung Chung5https://orcid.org/0000-0003-1449-8762Department of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, United StatesDepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, United StatesDepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, United StatesDepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, United StatesDepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, United StatesDepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, United StatesDental caries, a prevalent global health issue, results from complex bacterial interactions. In response to harmful stimuli, a desirable outcome for the tooth is the formation of tertiary dentin, a protective reparative process that generates new hard tissue. This reparative dentinogenesis is associated with significant inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs). Previously, we have demonstrated that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB), key mediators of neural functions, are activated during the DPSC-mediated dentin regeneration process. In this study, we further define the role of inflammation in this process and apply stem cell engineering to enhance dentin regeneration in injured teeth. Our data show that TrkB expression and activation in DPSCs rapidly increase during odontogenic differentiation, further amplified by inflammatory inducers and mediators such as tumor necrosis factor alpha (TNFα), lymphotoxin-alpha, and lipopolysaccharide. An in vivo dentin formation assessment was conducted using a mouse pulp-capping/caries model, where Clustered Regularly Interspaced Short Palindromic Repeats-engineered DPSCs overexpressing BDNF were transplanted into inflamed pulp tissue. This transplantation significantly enhanced dentin regeneration in injured teeth. To further explore potential downstream pathways, we conducted transcriptomic profiling of TNFα-treated DPSCs, both with and without TrkB antagonist cyclotraxin-B. The results revealed significant changes in gene expression related to immune response, cytokine signaling, and extracellular matrix interactions. Taken together, our study advances our understanding of the role of BDNF in dental tissue engineering using DPSCs and identifies potential therapeutic avenues for improving dental tissue repair and regeneration strategies.https://elifesciences.org/articles/105153human stem cellmouse transplantationstem cell engineering |
| spellingShingle | Ji Hyun Kim Muhammad Irfan Sreelekshmi Sreekumar Atsawasuwan Phimon Stephanie Kim Seung Chung CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth eLife human stem cell mouse transplantation stem cell engineering |
| title | CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth |
| title_full | CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth |
| title_fullStr | CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth |
| title_full_unstemmed | CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth |
| title_short | CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth |
| title_sort | crispr edited dpscs constitutively expressing bdnf enhance dentin regeneration in injured teeth |
| topic | human stem cell mouse transplantation stem cell engineering |
| url | https://elifesciences.org/articles/105153 |
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