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Journal of Periodontal Research Aug 2023Periodontitis is a chronic inflammatory disease involving soft and hard tissue destruction in the periodontal region. Cannabidiol (CBD) is a natural compound isolated...
BACKGROUND AND OBJECTIVE
Periodontitis is a chronic inflammatory disease involving soft and hard tissue destruction in the periodontal region. Cannabidiol (CBD) is a natural compound isolated from cannabis, which has the effect of inhibiting inflammation. However, the role of CBD in periodontitis remains unclear. The aim of this study was to investigate the anti-inflammatory effects and osteoprotective actions of CBD in periodontitis and its molecular mechanisms.
MATERIALS AND METHODS
After establishing the rat periodontitis model by ligatures, the specimens were processed for morphometric analysis by Micro-CT. The gingival tissues were collected, and the levels of TNF-α, IL-1β, and TLR4 were measured by enzyme-linked immunosorbent assay. LPS was used to induce the inflammatory response of human periodontal ligament cells (hPDLCs) in vitro. QPCR and western blot were carried out to detect the expression of related inflammatory cytokines and signaling pathways.
RESULTS
Cannabidiol significantly inhibits bone loss in experimental rat periodontitis models. CBD downregulated the pro-inflammatory mediator TNF-α, related to the decrease of TLR4 protein expression. Overexpression of TNF-α and TLR4 caused by LPS in hPDLCs. CBD inactivated the TLR4/NF-κB signaling pathway by inhibiting TLR-4 expression and p65 NF-κB phosphorylation. CBD can be considered as a therapeutic agent for periodontitis.
CONCLUSION
Our study demonstrated that CBD attenuates ligature-induced periodontitis in rats and LPS-induced inflammation in hPDLCs by inhibiting TLR4/NF-κB pathway activation. It indicates that topical CBD application is effective in treating periodontitis.
Topics: Humans; Rats; Animals; NF-kappa B; Cannabidiol; Tumor Necrosis Factor-alpha; Lipopolysaccharides; Toll-Like Receptor 4; Inflammation; Periodontitis
PubMed: 37143211
DOI: 10.1111/jre.13118 -
International Dental Journal Jun 2024The prevalence of diabetes mellitus (DM), a major chronic disease and a leading cause of death and disability around the world, is rising. According to the latest data,... (Review)
Review
The prevalence of diabetes mellitus (DM), a major chronic disease and a leading cause of death and disability around the world, is rising. According to the latest data, the global prevalence of DM has increased to 463 million (9.3% of adults) in 2019 and is estimated to reach 700 million by 2045. Periodontal disease, result of periodontium inflammation, is a common, chronic disease and has long been considered one of the complications of DM. Moreover, literature reflects a spectrum of conflicting viewpoints on the effect of diabetic conditions on the implant treatment strategies. The current review aims to update the recent epidemiologic evidence regarding the relationship between DM and periodontal/peri-implant disease, emphasising the effects of glycaemic control on the severity of these diseases and describing the pathobiological mechanisms underlying this association. This review's findings indicate a bidirectional relationship between DM and periodontal/peri-implant disease and that this relationship seems causal, implying that controlling these two diseases might help prevent each other's incidence. Additionally, the severity of periodontal/peri-implant disease is directly related to metabolic control. Although patients with diabetes can obtain implant success similar to those in systemically healthy individuals, an increased risk of peri-implantitis has been reported in DM patients. Therefore, the importance of glycaemic control and maintaining proper oral hygiene cannot be overstated.
Topics: Humans; Peri-Implantitis; Periodontal Diseases; Diabetes Mellitus; Diabetes Complications; Dental Implants; Prevalence; Risk Factors
PubMed: 38614881
DOI: 10.1016/j.identj.2024.03.010 -
Nature Communications Jan 2024Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure,...
Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/β-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/β-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.
Topics: Animals; Mice; beta Catenin; Silicon; Porosity; Lithium; Silicic Acid; Nanowires; Dental Cementum
PubMed: 38216556
DOI: 10.1038/s41467-023-44581-5 -
Clinical and Experimental Dental... Oct 2023The current strategies to reconstruct lost peri-implant tissues due to the disease have been largely unpredictable. The aim of this conceptual review is to discuss... (Review)
Review
OBJECTIVES
The current strategies to reconstruct lost peri-implant tissues due to the disease have been largely unpredictable. The aim of this conceptual review is to discuss relevant biological and biomechanical challenges of applying reconstructive means to treat peri-implantitis. Additionally, opportunities to improve treatment predictability are presented.
MATERIAL AND METHODS
A narrative review was conducted to fulfill the aim.
RESULTS
The four interrelated negative conditions hampering effective reconstruction are: inferior tissue perfusion, unfavorable bone topography, ineffective surface treatment, and unstable wound. First, peri-implant tissues resemble scars with reduced cellularity and vascularity, coupled with the absence of the periodontal ligament plexuses and the avascular implant and biomaterials, maintaining primary closure is a challenge, which is critical for regeneration. Second, defect morphology and bone topography surrounding implants determine the reconstructive potential. Unfortunately, noncontained defects are frequently encountered, with a combination of suprabony (horizontal bone loss) and infrabony (vertical usually involving circumferential bone loss) defects. Third, current attempts for implant surface decontamination are insufficient due to inaccessible macrostructure and rough surfaces in the micro-scale. Histologic evaluation has shown bacteria aggregation and calcified deposits around implants. Lastly, wound stability is difficult to achieve due to inherent soft tissue biomechanical quality and quantity deficiencies and mobile bone particulates. Opportunities to tackle the abovementioned challenges include the use of novel imaging technologies, such as high-frequency dental ultrasound and laser speckle imaging to evaluate tissue perfusion, soft tissue quality/quantity, and bone topography pre-surgically. The use of the operating microscope could allow better visualization and removal of etiologic factors. Strategies to improve soft tissue quality may include preoperative control of soft tissue inflammation and the potential use of biologics. Methods such as fixation to stabilize the biomaterials could be beneficial.
CONCLUSIONS
A more nuanced understanding of the current challenges and opportunities can lead to more effective preoperative and postoperative care protocols, ultimately improving the success rate of reconstructive procedures.
Topics: Humans; Peri-Implantitis; Dental Implants; Inflammation; Biocompatible Materials
PubMed: 37735844
DOI: 10.1002/cre2.788 -
International Journal of Oral Science Feb 2024The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate...
The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune-bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNA-sequencing analysis on mouse periodontal lesions and showed that neutrophil-osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.
Topics: Humans; Mice; Animals; Neutrophils; Periodontitis; Cytokines; Alveolar Bone Loss; Osteogenesis; RANK Ligand
PubMed: 38413562
DOI: 10.1038/s41368-023-00275-8 -
International Journal of Oral Science Jan 2024Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses....
Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1 mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Topics: Animals; Humans; Mice; Rats; Bone Remodeling; Caspase 1; Periodontal Ligament; Pyroptosis; Tooth Movement Techniques
PubMed: 38221531
DOI: 10.1038/s41368-023-00268-7 -
The European Journal of General Practice Dec 2024Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including... (Review)
Review
Periodontal diseases and cardiovascular diseases, diabetes, and respiratory diseases: Summary of the consensus report by the European Federation of Periodontology and WONCA Europe.
BACKGROUND
Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing.
OBJECTIVES
To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD).
METHODS
The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings.
RESULTS
Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors.
CONCLUSION
Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.
Topics: Humans; Noncommunicable Diseases; Cardiovascular Diseases; Consensus; Periodontal Diseases; Periodontitis; Diabetes Mellitus; Respiratory Tract Diseases; Europe
PubMed: 38511739
DOI: 10.1080/13814788.2024.2320120 -
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 -
Oral Diseases Apr 2024Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor... (Review)
Review
Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor populations of alveolar bone formation will provide valuable insights into regenerative approaches to clinical practice, such as endogenous regeneration and stem-cell-based tissue engineering therapies. Classically, MSCs residing in the bone marrow, periosteum, periodontal ligament (PDL), and even the gingiva are considered to be osteogenic progenitors. Furthermore, the contributions of MSCs expressing specific markers, including Gli1, Axin2, PTHrP, LepR, and α-SMA, to alveolar bone formation have been studied using cell lineage tracing and gene knockout models. In this review, we describe the MSCs/progenitors of alveolar bone and the biological properties of different subpopulations of MSCs involved in alveolar bone development, remodeling, injury repair, and regeneration.
Topics: Humans; Mesenchymal Stem Cells; Periodontium; Osteogenesis; Periodontitis; Periodontal Ligament; Animals
PubMed: 36648363
DOI: 10.1111/odi.14507 -
ACS Applied Materials & Interfaces Sep 2023Periodontal disease is a multifactorial, bacterially induced inflammatory condition characterized by the progressive destruction of periodontal tissues. The successful...
Periodontal disease is a multifactorial, bacterially induced inflammatory condition characterized by the progressive destruction of periodontal tissues. The successful nonsurgical treatment of periodontitis requires multifunctional technologies offering antibacterial therapies and promotion of bone regeneration simultaneously. For the first time, in this study, an injectable piezoelectric hydrogel (PiezoGEL) was developed after combining gelatin methacryloyl (GelMA) with biocompatible piezoelectric fillers of barium titanate (BTO) that produce electrical charges when stimulated by biomechanical vibrations (e.g., mastication, movements). We harnessed the benefits of hydrogels (injectable, light curable, conforms to pocket spaces, biocompatible) with the bioactive effects of piezoelectric charges. A thorough biomaterial characterization confirmed piezoelectric fillers' successful integration with the hydrogel, photopolymerizability, injectability for clinical use, and electrical charge generation to enable bioactive effects (antibacterial and bone tissue regeneration). PiezoGEL showed significant reductions in pathogenic biofilm biomass (∼41%), metabolic activity (∼75%), and the number of viable cells (∼2-3 log) compared to hydrogels without BTO fillers in vitro. Molecular analysis related the antibacterial effects to be associated with reduced cell adhesion (downregulation of and ) and increased oxidative stress (upregulation of ) genes. Moreover, PiezoGEL significantly enhanced bone marrow stem cell (BMSC) viability and osteogenic differentiation by upregulating , and . In vivo, PiezoGEL effectively reduced periodontal inflammation and increased bone tissue regeneration compared to control groups in a mice model. Findings from this study suggest PiezoGEL to be a promising and novel therapeutic candidate for the treatment of periodontal disease nonsurgically.
Topics: Animals; Mice; Hydrogels; Osteogenesis; Periodontal Diseases; Periodontium; Anti-Bacterial Agents
PubMed: 37672788
DOI: 10.1021/acsami.3c08336