Regeneration of the cementum and periodontal ligament using local BDNF delivery in class II furcation defects

Jimbo, Ryo; Singer, Jessica; Tovar, Nick; Marin, Charles; Neiva, Rodrigo; Bonfante, Estevam A.; Contamin, Hugues; Coelho, Paulo G.

doi:10.1002/jbm.b.33977

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…BDNF is another growth factor also associated with periodontal regeneration 29,40 and the regulation of cell functions 5,29 . In our study, BDNF only upregulated ETV1 , even though it affected the expression of most examined miRNAs.…”

Section: Discussionmentioning

confidence: 43%

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Iwata

Mizuno

Nagahara

et al. 2021

Journal of Periodontology

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Background Cytokines play key roles in stimulating periodontal regeneration; however, their exact mechanisms of action remain unclear. Mesenchymal stem cells (MSCs) are multipotent cells that have self‐renewal abilities and can differentiate into periodontal tissues such as bone, cementum, and periodontal ligaments following transplantation, like periodontal progenitor cells. Here, we used MSCs to identify the regulatory genes induced by periodontal regenerative cytokines. Methods Human MSCs (hMSCs) were cultured under conditions of periodontal regenerative cytokine stimulation or silencing of undifferentiated hMSC transcription factors. To characterize the changes associated with periodontal regenerative cytokine‐regulated microRNAs (miRNAs), miRNA, and mRNA expression was evaluated using miRNA arrays and quantitative real‐time polymerase chain reaction, respectively. One of the identified miRNAs, miR‐628‐5p, was then overexpressed or suppressed in hMSCs during osteogenesis; the effect of these changes on osteogenesis was investigated. Results Cytokine‐stimulated MSCs showed characteristic miRNA profiles and mRNA levels of undifferentiated hMSC transcription factors ETV1, SOX11, and GATA6. Next, we silenced these transcription factors in MSCs and examined the miRNA profiles. The levels of miR‐628‐5p were decreased upon all cytokine treatments and were increased upon silencing of ETV1, SOX11, and GATA6. Overexpression of miR‐628‐5p suppressed osteogenesis; however, its inhibition enhanced OPN, ALP, OC, BMP2, and RUNX2 mRNA levels, and bone matrix mineralization, but not OSX mRNA or ALP activity. Conclusions miR‐628‐5p negatively regulates MSC stemness during periodontal regeneration. Periodontal regenerative cytokines act as miR‐628‐5p suppressors to support periodontal regeneration. Thus, selection of effective cytokines for different MSCs, based on miRNA profiling, is important for advancing regenerative therapies.

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Section: Discussionmentioning

confidence: 43%

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Iwata

Mizuno

Nagahara

et al. 2021

Journal of Periodontology

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“…Epithelial down growth are not favorable repair phenomena, as they interfere with the completion of periodontal tissue regeneration. BDNF induces cementogenesis 20,32 and OPN expression in periodontal tissue; 20,22 moreover, BDNF regulates cell growth of gingival epithelial cells. 33,34 Therefore, newly formed cementum covering with denuded root surface might prevent epithelial downgrowth in early regenerative phase.…”

Section: Discussionmentioning

confidence: 99%

Periodontal tissue regeneration with cementogenesis after application of brain‐derived neurotrophic factor in 3‐wall inflamed intra‐bony defect

Kiyota,

Iwata,

Hasegawa

et al. 2024

J of Periodontal Research

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ObjectiveThe purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3‐wall intra‐bony defects.BackgroundBrain‐derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non‐neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)‐related proteins and proliferation of human periodontal ligament cells.MethodsSix weeks after extraction of mandibular first and third premolars, 3‐wall intra‐bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 μg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)‐positive cells were evaluated by immunohistochemical analysis.ResultsTwo weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA‐positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN‐positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose‐dependently increased.ConclusionThese findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3‐wall intra‐bony defects.

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“…For example, NGF has been incorporated into bone scaffolds to treat rat cranial defects, showing an increase in innervation but limited new bone formation. , NGF delivery via alginate hydrogels has also been used to increase bone and cementum formation in periodontal defects . Local injection of SP promoted bone formation during mandibular distraction osteogenesis in rats, and BDNF delivery from collagen sponges , or using hyaluronic acid hydrogels ,− led to increased bone, PDL, and cementum formation compared to scaffold controls. Galanin-loaded collagen sponges promoted bone formation in inflammatory periodontal defects .…”

Section: Current Craniofacial Tissue Regenerative Approaches That Tar...mentioning

confidence: 99%

Tissue Engineered Neurovascularization Strategies for Craniofacial Tissue Regeneration

Fraser

Mereness

et al. 2021

ACS Appl. Bio Mater.

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Craniofacial tissue injuries, diseases, and defects, including those within bone, dental, and periodontal tissues and salivary glands, impact an estimated 1 billion patients globally. Craniofacial tissue dysfunction significantly reduces quality of life, and successful repair of damaged tissues remains a significant challenge. Blood vessels and nerves are colocalized within craniofacial tissues and act synergistically during tissue regeneration. Therefore, the success of craniofacial regenerative approaches is predicated on successful recruitment, regeneration, or integration of both vascularization and innervation. Tissue engineering strategies have been widely used to encourage vascularization and, more recently, to improve innervation through host tissue recruitment or prevascularization/innervation of engineered tissues. However, current scaffold designs and cell or growth factor delivery approaches often fail to synergistically coordinate both vascularization and innervation to orchestrate successful tissue regeneration. Additionally, tissue engineering approaches are typically investigated separately for vascularization and innervation. Since both tissues act in concert to improve craniofacial tissue regeneration outcomes, a revised approach for development of engineered materials is required. This review aims to provide an overview of neurovascularization in craniofacial tissues and strategies to target either process thus far. Finally, key design principles are described for engineering approaches that will support both vascularization and innervation for successful craniofacial tissue regeneration.

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Regeneration of the cementum and periodontal ligament using local BDNF delivery in class II furcation defects

Cited by 11 publications

References 24 publications

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Periodontal tissue regeneration with cementogenesis after application of brain‐derived neurotrophic factor in 3‐wall inflamed intra‐bony defect

Tissue Engineered Neurovascularization Strategies for Craniofacial Tissue Regeneration

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