BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells
The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brai...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/14/1851 |
| _version_ | 1827733533118955520 |
|---|---|
| author | Ji-Hyun Kim Muhammad Irfan Md Akil Hossain Anne George Seung Chung |
| author_facet | Ji-Hyun Kim Muhammad Irfan Md Akil Hossain Anne George Seung Chung |
| author_sort | Ji-Hyun Kim |
| collection | DOAJ |
| description | The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs. |
| first_indexed | 2024-03-11T01:12:35Z |
| format | Article |
| id | doaj.art-60e4df085c954e249cb4d20bac528734 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:12:35Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-60e4df085c954e249cb4d20bac5287342023-11-18T18:46:04ZengMDPI AGCells2073-44092023-07-011214185110.3390/cells12141851BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem CellsJi-Hyun Kim0Muhammad Irfan1Md Akil Hossain2Anne George3Seung Chung4Department of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USAThe odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs.https://www.mdpi.com/2073-4409/12/14/1851BDNFTrkBdentinogenesisDPSCsinflammation |
| spellingShingle | Ji-Hyun Kim Muhammad Irfan Md Akil Hossain Anne George Seung Chung BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells Cells BDNF TrkB dentinogenesis DPSCs inflammation |
| title | BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells |
| title_full | BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells |
| title_fullStr | BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells |
| title_full_unstemmed | BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells |
| title_short | BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells |
| title_sort | bdnf trkb is a crucial regulator in the inflammation mediated odontoblastic differentiation of dental pulp stem cells |
| topic | BDNF TrkB dentinogenesis DPSCs inflammation |
| url | https://www.mdpi.com/2073-4409/12/14/1851 |
| work_keys_str_mv | AT jihyunkim bdnftrkbisacrucialregulatorintheinflammationmediatedodontoblasticdifferentiationofdentalpulpstemcells AT muhammadirfan bdnftrkbisacrucialregulatorintheinflammationmediatedodontoblasticdifferentiationofdentalpulpstemcells AT mdakilhossain bdnftrkbisacrucialregulatorintheinflammationmediatedodontoblasticdifferentiationofdentalpulpstemcells AT annegeorge bdnftrkbisacrucialregulatorintheinflammationmediatedodontoblasticdifferentiationofdentalpulpstemcells AT seungchung bdnftrkbisacrucialregulatorintheinflammationmediatedodontoblasticdifferentiationofdentalpulpstemcells |