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Journal of Periodontal Research Apr 2024To estimate whether genetically proxied periodontitis causally impacts the brain cortical structure using Mendelian randomization (MR). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate whether genetically proxied periodontitis causally impacts the brain cortical structure using Mendelian randomization (MR).
BACKGROUND
Periodontitis is one of the most prevalent inflammatory conditions globally, and emerging evidence has indicated its influences on distal organs, including the brain, whose disorders are always accompanied by magnetic resonance imaging (MRI)-identified brain cortical changes. However, to date, no available evidence has revealed the association between periodontitis and brain cortical structures.
METHODS
The instrumental variables (IVs) were adopted from previous genome-wide association study (GWAS) studies and meta-analyses of GWAS studies of periodontitis from 1844 to 5266 cases and 8255 to 12 515 controls. IVs were linked to GWAS summary data of 51 665 patients from the ENIGMA Consortium, assessing the impacts of genetically proxied periodontitis on the surficial area (SA) or the cortical thickness (TH) of the global and 34 MRI-identified functional regions of the brain. Inverse-variance weighted was used as the primary estimate; the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy.
RESULTS
Genetically proxied periodontitis affects the SA of the medial orbitofrontal cortex, the lateral orbitofrontal cortex, the inferior temporal cortex, the entorhinal cortex, and the temporal pole, as well as the TH of the entorhinal. No pleiotropy was detected.
CONCLUSIONS
Periodontitis causally influences the brain cortical structures, implying the existence of a periodontal tissue-brain axis.
Topics: Humans; Brain; Genome-Wide Association Study; Mendelian Randomization Analysis; Periodontitis; Periodontium
PubMed: 38059384
DOI: 10.1111/jre.13222 -
Activation of receptor-interacting protein 3-mediated necroptosis accelerates periodontitis in mice.Oral Diseases May 2024To investigate the involvement and role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in periodontitis.
OBJECTIVE
To investigate the involvement and role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in periodontitis.
METHODS
A periodontitis murine model was established by oral infection with Porphyromonas gingivalis, and activation of necroptosis pathway was identified by immunohistochemistry. Adeno-associated virus was used to knock down Rip3 and the effect of Rip3 knockdown on periodontal inflammation was examined by Micro-CT, qRT-PCR and histological staining. In vitro, P. gingivalis-LPS was used to infect fibroblast cell line L929 and siRNA was used to knock down Rip3. Necroptosis pathway signalling and inflammation in cells were detected by cell viability and death assay, Western Blot, qRT-PCR and immunofluorescence analysis.
RESULTS
Phosphorylation of RIP3 and mixed lineage kinase domain-like protein (MLKL) was increased in the periodontal ligament of mice infected with P. gingivalis. RIP3 knockdown reduced osteoclastogenesis and inflammatory cytokines in the periodontal area, and alleviated alveolar bone loss in vivo. In vitro, P. gingivalis-LPS-induced RIP3-mediated necroptosis in L929 cells, and knockdown of RIP3 by siRNA decreased the expression of inflammatory cytokines.
CONCLUSION
RIP3-mediated necroptosis is activated in periodontitis and blocking necroptosis alleviates disease progression, indicating that RIP3 may be a potential target for periodontitis treatment.
Topics: Animals; Necroptosis; Receptor-Interacting Protein Serine-Threonine Kinases; Mice; Periodontitis; Porphyromonas gingivalis; Disease Models, Animal; Cell Line; Mice, Inbred C57BL; Male; Bacteroidaceae Infections; Protein Kinases; Gene Knockdown Techniques; Periodontal Ligament; Phosphorylation; Cytokines; Alveolar Bone Loss
PubMed: 37518945
DOI: 10.1111/odi.14693 -
Oral Diseases Oct 2023Periodontitis is an inflammatory disease characterized by alveolar bone loss. Periodontal ligament stem cells (PDLSCs) have osteogenic differentiation potential, which... (Review)
Review
Periodontitis is an inflammatory disease characterized by alveolar bone loss. Periodontal ligament stem cells (PDLSCs) have osteogenic differentiation potential, which can be influenced by epigenetics regulation in periodontitis. Therefore, this review aimed to shed light on the role of different epigenetic mechanisms in the osteogenic differentiation of PDLSCs and to consider the prospects of their possible therapeutic applications in periodontitis. Databases MEDLINE (through PubMed) and Web of Science were searched for the current knowledge of epigenetics in osteogenic differentiation of PDLSCs using the keywords "periodontal ligament stem cells", "epigenetic regulation", "epigenetics", "osteogenic differentiation", and "osteogenesis". All studies introducing epigenetic regulation and PDLSCs were retrieved. This review shows that epigenetic factors like DNMT, KDM6A, HDACi, some miRNAs, and lncRNAs can induce the osteogenic differentiation of PDLSCs in the noninflammatory microenvironment. However, the osteogenic differentiation of PDLSCs is inhibited in the inflammatory microenvironment through the upregulated DNA methylation of osteogenesis-related genes and specific changes in histone modification and noncoding RNA. Epigenetics of osteogenic differentiation of PDLSCs in inflammation exhibits the contrary effect compared with a noninflammatory environment. The application of epigenetic drugs to regulate the abnormal epigenetic status in periodontitis and focus on alveolar bone regeneration is promising.
Topics: Humans; Osteogenesis; Periodontal Ligament; Epigenesis, Genetic; Periodontitis; Stem Cells; Cell Differentiation; Cells, Cultured
PubMed: 36582112
DOI: 10.1111/odi.14491 -
Molecular Biology Reports Dec 2023MSC-based therapeutic strategies have proven to be incredibly effective. Robust self-renewal, multilineage differentiation, and potential for tissue regeneration and... (Review)
Review
MSC-based therapeutic strategies have proven to be incredibly effective. Robust self-renewal, multilineage differentiation, and potential for tissue regeneration and disease treatments are all features of MSCs isolated from oral tissue. Human exfoliated deciduous teeth, dental follicles, dental pulp, apical papilla SCs, and alveolar bone are the primary sources of oral MSC production. The early immunoinflammatory response is the first stage of the healing process. Oral MSCs can interact with various cells, such as immune cells, revealing potential immunomodulatory regulators. They also have strong differentiation and regeneration potential. Therefore, a ground-breaking strategy would be to research novel immunomodulatory approaches for treating disease and tissue regeneration that depend on the immunomodulatory activities of oral MSCs during tissue regeneration.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Gingiva; Mesenchymal Stem Cells; Cell Differentiation; Cells, Cultured
PubMed: 37904011
DOI: 10.1007/s11033-023-08826-2 -
Dental Materials : Official Publication... Oct 2023Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial...
OBJECTIVES
Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo.
METHODS
hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste. Five groups were tested: (1) CPC control; (2) CPC + hPDLSC-fibers + 0% Met (CPC + hPDLSCs + 0%Met); (3) CPC + hPDLSC-fibers + 0.1% Met (CPC + hPDLSCs + 0.1%Met); (4) CPC + hPDLSC-fibers + 0.2% Met (CPC + hPDLSCs + 0.2%Met); (5) CPC + hPDLSC-fibers + 0.4% Met (CPC + hPDLSCs + 0.4%Met). The injectability, mechanical properties, metformin release, and hPDLSC osteogenic differentiation and bone mineral were determined in vitro. A rat cranial defect model was used to evaluate new bone formation.
RESULTS
The novel construct had good injectability and physical properties. Alginate fibers degraded in 7 days and released hPDLSCs, with 5-fold increase of proliferation (p<0.05). The ALP activity and mineral synthesis of hPDLSCs were increased by Met delivery (p<0.05). Among all groups, CPC+hPDLSCs+ 0.1%Met showed the greatest cell mineralization and osteogenesis, which were 1.5-10 folds those without Met (p<0.05). Compared to CPC control, CPC+hPDLSCs+ 0.1%Met enhanced bone regeneration in rats by 9 folds, and increased vascularization by 3 folds (p<0.05).
CONCLUSIONS
The novel injectable construct with hPDLSC and Met encapsulation demonstrated excellent efficacy for bone regeneration and vascularization in vivo in an animal model. CPC+hPDLSCs+ 0.1%Met is highly promising for dental and craniofacial applications.
Topics: Rats; Humans; Animals; Osteogenesis; Tissue Scaffolds; Periodontal Ligament; Metformin; Bone Regeneration; Stem Cells; Cell Differentiation; Calcium Phosphates; Alginates; Cells, Cultured
PubMed: 37574338
DOI: 10.1016/j.dental.2023.07.008 -
Journal of Stomatology, Oral and... Sep 2023The aim of this study is to investigate the pneumatization type of the palatal process (PTP) and angular and distance measurements of neighbouring structures on cone...
PURPOSE
The aim of this study is to investigate the pneumatization type of the palatal process (PTP) and angular and distance measurements of neighbouring structures on cone beam computed tomography (CBCT) images.
MATERIALS AND METHODS
400 maxillary sinuses (MS) of 200 patients (96 female; 104 male; mean age: 43.2) were retrospectively evaluated. PTP was divided into three as types 1,2 and 3 and evaluated at distances 4, 8, 16, and 24 mm posterior to incisive foramen. The sinus and alveolar ridge height, palatonasal recess angle (PRA) and palatal junction angle (PJA) were also measured and recorded.
RESULTS
PTP I (101, 25.3%) was the most frequent type, followed by PTP II (95, 23.8%), and the least was PTP III (4, 1%). In patients with PTP I, the alveolar ridge height in the 4 mm and 8 mm group was significantly higher than in the patients with PTP II and III (p<0.05). In patients with PTP I, PRA in the 4 mm and 16 mm groups was significantly higher than in patients with PTP II and III (p<0.05). Sinus and alveolar ridge height, PRA and PJA did not differ significantly between the right and left sides in the 4 mm, 8 mm, 16 mm, and 24 mm groups (p>0.05).
CONCLUSION
Knowing the anatomy of the MS is very important for a successful surgical procedure in this area. Anatomy and pathology of the MS can be understood more clearly in CBCT.
Topics: Humans; Male; Female; Adult; Retrospective Studies; Alveolar Process; Maxillary Sinus; Cone-Beam Computed Tomography; Palate
PubMed: 36921841
DOI: 10.1016/j.jormas.2023.101432 -
Scientific Reports Jan 2024Several studies have demonstrated that exosomes (Exos) are involved in the regulation of macrophage polarization and osteoclast differentiation. However, the...
Several studies have demonstrated that exosomes (Exos) are involved in the regulation of macrophage polarization and osteoclast differentiation. However, the characteristics as well as roles of exosomes from human periodontal ligament cells (hPDLCs-Exos) in M1/M2 macrophage polarization and osteoclast differentiation remain unclear. Here, periodontal ligament cells were successfully extracted by method of improved Type-I collagen enzyme digestion. hPDLCs-Exos were extracted by ultracentrifugation. hPDLCs-Exos were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting (WB). Osteoclast differentiation was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), WB and tartrate-resistant acid phosphatase (TRAP) staining. M1/M2 macrophage polarization were evaluated by RT-qPCR and WB. The results showed hPDLCs-Exos promoted osteoclast differentiation and M2 macrophage polarization, but inhibited M1 macrophage polarization. Moreover, M1 macrophages inhibited osteoclast differentiation, whereas M2 macrophages promoted osteoclast differentiation. It has shown that hPDLCs-Exos promoted osteoclast differentiation by inhibiting M1 and promoting M2 macrophage polarization.
Topics: Humans; Exosomes; Periodontal Ligament; Osteoclasts; Macrophages; Cells, Cultured; MicroRNAs
PubMed: 38233593
DOI: 10.1038/s41598-024-52073-9 -
BMC Oral Health Sep 2023The effect of attachment positions on anchorage has not been fully explored. The aim of the present study is to analyze the effect of overtreatment with different...
BACKGROUND
The effect of attachment positions on anchorage has not been fully explored. The aim of the present study is to analyze the effect of overtreatment with different anchorage positions on maxillary anchorage enhancement with clear aligners in extraction cases.
METHODS
Models of the maxilla and maxillary dentition were constructed and imported into SOLIDWORKS software to create periodontal ligament (PDL), clear aligners, and attachments. Attachment positions on second premolars included: without attachment (WOA), buccal attachment (BA), and bucco-palatal attachment (BPA). Overtreatment degrees were divided into five groups (0°, 1°, 2°, 3°, 4°) and added on the second premolars. The calculation and analysis of the displacement trends and stress were performed using ANSYS software.
RESULTS
Distal tipping and extrusion of the canines, and mesial tipping and intrusion of the posterior teeth occurred during retraction. A strong anchorage was achieved in cases of overtreatment of 2.8° with BA and 2.4° with BPA. Moreover, the BPA showed the best in achieving bodily control of the second premolars. When the overtreatment was performed, the canines and first molars also showed reduced tipping trends with second premolars attachments. And the stress on the PDL and the alveolar bone was significantly relieved and more evenly distributed in the BPA group.
CONCLUSIONS
Overtreatment is an effective means for anchorage enhancement. However, the biomechanical effect of overtreatment differs across attachment positions. The BPA design performs at its best for stronger overtreatment effects with fewer adverse effects.
Topics: Humans; Finite Element Analysis; Maxilla; Periodontal Ligament; Overtreatment; Orthodontic Appliances, Removable
PubMed: 37749548
DOI: 10.1186/s12903-023-03340-0 -
International Journal of Molecular... Jan 2024Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, periodontal ligament, cementum, and alveolar bone. It arises from the... (Review)
Review
Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, periodontal ligament, cementum, and alveolar bone. It arises from the complex interplay between pathogenic oral bacteria and host immune response. Contrary to the previous view of "energy factories", mitochondria have recently been recognized as semi-autonomous organelles that fine-tune cell survival, death, metabolism, and other functions. Under physiological conditions, periodontal tissue cells participate in dynamic processes, including differentiation, mineralization, and regeneration. These fundamental activities depend on properly functioning mitochondria, which play a crucial role through bioenergetics, dynamics, mitophagy, and quality control. However, during the initiation and progression of periodontitis, mitochondrial quality control is compromised due to a range of challenges, such as bacterial-host interactions, inflammation, and oxidative stress. Currently, mounting evidence suggests that mitochondria dysfunction serves as a common pathological mechanism linking periodontitis with systemic conditions like type II diabetes, obesity, and cardiovascular diseases. Therefore, targeting mitochondria to intervene in periodontitis and multiple associated systemic diseases holds great therapeutic potential. This review provides advanced insights into the interplay between mitochondria, periodontitis, and associated systemic diseases. Moreover, we emphasize the significance of diverse therapeutic modulators and signaling pathways that regulate mitochondrial function in periodontal and systemic cells.
Topics: Humans; Diabetes Mellitus, Type 2; Periodontitis; Inflammation; Periodontium; Mitochondrial Diseases
PubMed: 38256098
DOI: 10.3390/ijms25021024 -
Dental Traumatology : Official... Apr 2024Frondoside A is a sea cucumber extract which is well known for its anti-inflammatory and immunomodulatory properties. The purpose of this study was to evaluate the...
BACKGROUND/AIM
Frondoside A is a sea cucumber extract which is well known for its anti-inflammatory and immunomodulatory properties. The purpose of this study was to evaluate the effect of Frondoside A application in the alveolar socket on inflammatory responses after delayed replantation in rat teeth.
MATERIALS AND METHODS
Human periodontal ligament cells were cultured and exposed to Frondoside A. Cell-counting kit-8 assay was performed to evaluate the cell viability and nitric oxide assay was performed to assess the anti-inflammatory effect of Frondoside A. Molars were extracted from 32 Sprague-Dawley rats and randomly divided into control and Frondoside A groups. After 30 min of extra-oral dry time, molars were replanted. In the Frondoside A group, Frondoside A solution was applied in the alveolar socket before replantation. The animals were sacrificed after 28 days and histologically and immunohistochemically evaluated.
RESULTS
0.5 μM Frondoside A showed higher cellular viability at 6 h and lower production of nitric oxide compared with other Frondoside A solutions (p < .05). The Frondoside A group demonstrated lower inflammatory resorption scores in both middle 1/3 and apical 1/3 of root compared to the control group (p < .05). The Frondoside A group showed lower levels of expression in both cathepsin K and CD45 compared with the control group (p < .05).
CONCLUSIONS
Within the limits of this study, intra-alveolar delivery of Frondoside A alleviates inflammatory root resorption in delayed replantation of rat teeth.
Topics: Rats; Animals; Humans; Tooth Replantation; Nitric Oxide; Rats, Sprague-Dawley; Root Resorption; Periodontal Ligament; Anti-Inflammatory Agents; Tooth Root; Glycosides; Triterpenes
PubMed: 37731288
DOI: 10.1111/edt.12891