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JDR Clinical and Translational Research Jul 2024Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points...
INTRODUCTION
Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points emanate from cross-sectional studies. Orthodontic treatment is an elective procedure that can be exploited to prospectively examine clinically relevant longitudinal changes in the composition and function of the supragingival microbiome.
METHODS
A longitudinal cohort study was conducted among 24 adolescent orthodontic patients who underwent saliva and plaque sampling and clinical examinations at time points: before fixed appliance bonding and at 1, 6, and 12 wk thereafter. Clinical indices included bleeding on probing (BOP), mean gingival index (GI), probing depths (PDs), and plaque index (PI). To study the biologically (i.e., transcriptionally) active microbial communities, RNA was extracted from plaque and saliva for RNA sequencing and microbiome bioinformatics analysis. Longitudinal changes in microbiome beta diversity were examined using PERMANOVA tests, and the relative abundance of microbial taxa was measured using Kruskal-Wallis tests, Wilcoxon rank-sum tests, and negative binomial and zero-inflated mixed models.
RESULTS
Clinical measures of oral health deteriorated over time-the proportion of sites with GI and PI ≥1 increased by over 70% between prebonding and 12 wk postbonding while the proportion of sites with PD ≥4 mm increased 2.5-fold. , a health-associated species that antagonizes cariogenic pathogens, showed a lasting decrease in relative abundance during orthodontic treatment. Contrarily, caries- and periodontal disease-associated taxa, including , , and , increased in abundance after bonding. Relative abundances of and in prebonding saliva predicted elevated BOP 12 wk postbonding, whereas was associated with lower BOP.
CONCLUSIONS
This study offers insights into longitudinal community and species-specific changes in the supragingival microbiome transcriptome during fixed orthodontic treatment, advancing our understanding of microbial dysbioses and identifying targets of future health-promoting clinical investigations.
KNOWLEDGE TRANSFER STATEMENT
Bonding braces was associated with subsequent changes in the oral microbiome characterized by increases in disease-associated species, decreases in health-associated species, and worsened clinical measures of oral health.
Topics: Humans; Longitudinal Studies; Adolescent; Male; Biofilms; Female; Microbiota; Saliva; Transcriptome; Dental Plaque; Orthodontics; Gingiva; Child
PubMed: 37876206
DOI: 10.1177/23800844231199393 -
Frontiers in Oral Health 2023Periodontitis is delineated by a dysbiotic microbiome at sites of lesions accompanied by a dysregulated persistent inflammatory response that undermines the integrity of...
INTRODUCTION
Periodontitis is delineated by a dysbiotic microbiome at sites of lesions accompanied by a dysregulated persistent inflammatory response that undermines the integrity of the periodontium. The interplay of the altered microbial ecology and warning signals from host cells would be a critical feature for maintaining or re-establishing homeostasis in these tissues.
METHODS
This study used a nonhuman primate model () with naturally-occurring periodontitis ( = 34) and experimental ligature-induced periodontitis ( = 36) to describe the features of gene expression for an array of damage-associate molecular patterns (DAMPs) or alarmins within the gingival tissues. The animals were age stratified into: ≤3 years (Young), 7-12 years (Adolescent), 12-15 years (Adult) and 17-23 years (Aged). Gingival tissue biopsies were examined via microarray. The analysis focused on 51 genes representative of the DAMPs/alarmins family of host cell warning factors and 18 genes associated with tissue destructive processed in the gingival tissues. Bacterial plaque samples were collected by curette sampling and 16S rRNA gene sequences used to describe the oral microbiome.
RESULTS
A subset of DAMPs/alarmins were expressed in healthy and naturally-occurring periodontitis tissues in the animals and suggested local effects on gingival tissues leading to altered levels of DAMPs/alarmins related to age and disease. Significant differences from adult healthy levels were most frequently observed in the young and adolescent animals with few representatives in this gene array altered in the healthy aged gingival tissues. Of the 51 target genes, only approximately ⅓ were altered by ≥1.5-fold in any of the age groups of animals during disease, with those increases observed during disease initiation. Distinctive positive and negative correlations were noted with the DAMP/alarmin gene levels and comparative expression changes of tissue destructive molecules during disease across the age groups. Finally, specific correlations of DAMP/alarmin genes and relative abundance of particular microbes were observed in health and resolution samples in younger animals, while increased correlations during disease in the older groups were noted.
CONCLUSIONS
Thus, using this human-like preclinical model of induced periodontitis, we demonstrated the dynamics of the activation of the DAMP/alarmin warning system in the gingival tissues that showed some specific differences based on age.
PubMed: 38098978
DOI: 10.3389/froh.2023.1320083 -
Pharmaceutics Aug 2023Dental tissues are composed of multiple tissues with complex organization, such as dentin, gingiva, periodontal ligament, and alveolar bone. These tissues have different... (Review)
Review
Dental tissues are composed of multiple tissues with complex organization, such as dentin, gingiva, periodontal ligament, and alveolar bone. These tissues have different mechanical and biological properties that are essential for their functions. Therefore, dental diseases and injuries pose significant challenges for restorative dentistry, as they require innovative strategies to regenerate damaged or missing dental tissues. Biomimetic bioconstructs that can effectively integrate with native tissues and restore their functionalities are desirable for dental tissue regeneration. However, fabricating such bioconstructs is challenging due to the diversity and complexity of dental tissues. This review provides a comprehensive overview of the recent developments in polymer-based tissue engineering and three-dimensional (3D) printing technologies for dental tissue regeneration. It also discusses the current state-of-the-art, focusing on key techniques, such as polymeric biomaterials and 3D printing with or without cells, used in tissue engineering for dental tissues. Moreover, the final section of this paper identifies the challenges and future directions of this promising research field.
PubMed: 37631331
DOI: 10.3390/pharmaceutics15082118 -
Minerva Dental and Oral Science Aug 2023A recent systematic review failed to identify one approach for alveolar ridge preservation with superior outcomes. The present case series aimed to evaluate the...
BACKGROUND
A recent systematic review failed to identify one approach for alveolar ridge preservation with superior outcomes. The present case series aimed to evaluate the dimensional changes of sites undergoing Biologically-oriented Alveolar Ridge Preservation (BARP).
METHODS
The sockets were filled with a collagen sponge up to 4-5 mm from the most coronal extensions of the crest. Xenograft particles were placed to fill the coronal part. In cases with a compromised buccal/lingual bone, an additional collagen sponge was interposed between the residual cortical bone plate and the mucoperiosteal flap. A collagen sponge was placed to cover the graft.
RESULTS
The study population consisted in 10 extraction sites. Mean change in bone width and vertical ridge position as observed from BARP to re-entry for implant placement were 1.3 mm (14.4%) and 0.6 mm, respectively. The mean distance between buccal and lingual flap healing by secondary intention shifted from 4.9 mm immediately after BARP to 1.8 mm at 2 weeks. No marked differences in the dimensional changes of alveolar ridge were observed between sites with intact or deficient buccal bone plate. All implants were successfully loaded at 2-3 months after placement. In one case, bone augmentation was required.
CONCLUSIONS
The stratification of materials proposed in BARP-technique and the additional use of a resorbable device to stabilize graft particles at the buccal aspect provided the conditions for maintaining the ridge dimensions following tooth extraction comparable to the other technique of ARP, restricting the use of graft material to the most coronal portion of the socket.
Topics: Humans; Tooth Socket; Alveolar Bone Loss; Alveolar Process; Collagen; Wound Healing
PubMed: 37066894
DOI: 10.23736/S2724-6329.23.04776-9 -
Nature Communications Nov 2023Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis...
Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration therapy period. We apply the symbiotically integrating occlusive membrane to treat inflammatory-challenged cases in vivo, namely, the open and closed healing of canine premolars with severe periodontitis. We find that the membrane promotes symbiosis, prevents negative inflammatory responses, and improves cellular integration. Finally, we show that guided bone regeneration therapy with the symbiotically integrating occlusive membrane achieves fast healing of gingival soft tissue and alveolar bone.
Topics: Humans; Alveolar Bone Loss; Guided Tissue Regeneration, Periodontal; Wound Healing; Periodontitis; Gingiva; Membranes, Artificial; Bone Regeneration
PubMed: 38001080
DOI: 10.1038/s41467-023-43428-3 -
Advanced Healthcare Materials Oct 2023Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption....
Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N-acetyl-l-cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H O stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.
Topics: Mice; Humans; Animals; Reactive Oxygen Species; Kelch-Like ECH-Associated Protein 1; Acetylcysteine; NF-E2-Related Factor 2; Osteogenesis; Antioxidants; Oxidative Stress; Periodontitis; Bone Resorption; Homeostasis
PubMed: 37279380
DOI: 10.1002/adhm.202300890 -
European Journal of Dentistry May 2024Cells are the building blocks of all living organisms. The presence of cell junctions such as tight junctions, gap junctions, and anchoring junctions between cells play...
Cells are the building blocks of all living organisms. The presence of cell junctions such as tight junctions, gap junctions, and anchoring junctions between cells play a role in cell-to-cell communication in periodontal health and disease. A literature search was done in Scopus, PubMed, and Web of Science to gather information about the effect of cell junctions on periodontal health and disease. The presence of tight junction in the oral cavity helps in cell-to-cell adhesiveness and assists in the barrier function. The gap junctions help in controlling growth and development and in the cell signaling process. The presence of desmosomes and hemidesmosomes as anchoring junctions aid in mechanical strength and tissue integrity. Periodontitis is a biofilm-induced disease leading to the destruction of the supporting structures of the tooth. The structures of the periodontium possess multiple cell junctions that play a significant role in periodontal health and disease as well as periodontal tissue healing. This review article provides an insight into the role of cell junctions in periodontal disease and health, and offers concepts for development of therapeutic strategies through manipulation of cell junctions.
PubMed: 38049123
DOI: 10.1055/s-0043-1775726 -
Inflammation Oct 2023As a chronic inflammatory disease, periodontitis involves many biological processes including autophagy. At the same time, casein kinase 2 interacting protein-1 (CKIP-1)...
As a chronic inflammatory disease, periodontitis involves many biological processes including autophagy. At the same time, casein kinase 2 interacting protein-1 (CKIP-1) was reported to play a role in regulation of inflammation. But whether CKIP-1 and autophagy interact in periodontitis remains unclear. In this paper, our research team verified the levels of CKIP-1 expression and autophagy increase in the periodontal tissues of a ligature-induced periodontitis mouse model. And this result was also confirmed in Porphyromonas gingivalis (Pg)-induced human gingival fibroblasts (HGF) and human periodontal ligament cells (PDLC). We also showed the autophagy level in periodontal tissues is higher in Ckip-1 knockout (KO) mice than wild type (WT). At the same time, CKIP-1 knockdown lentivirus was used in PDLC and HGF, and it was found that silencing CKIP-1 significantly activated autophagy. Unfortunately, the regulatory role of autophagy in periodontitis is still unclear. Then, the autophagy agonist Rapamycin and inhibitor 3-MA were used in a periodontitis mouse model to investigate periodontal tissue destruction. We found the inflammation in periodontal tissue was reduced when autophagy activated. All these conclusions have been verified both in vivo and in vitro experiments. Finally, our research proved that silencing CKIP-1 reduces the expression of inflammatory cytokines in Pg-induced PDLC and HGF by regulating autophagy. Overall, a new role for CKIP-1 in regulating periodontal tissue inflammation was demonstrated in our study, and it is possible to treat periodontitis by targeting the CKIP-1 gene.
Topics: Mice; Animals; Humans; Inflammation; Periodontitis; Gingiva; Cytokines; Porphyromonas gingivalis; Autophagy; Carrier Proteins
PubMed: 37351817
DOI: 10.1007/s10753-023-01856-9 -
BDJ Open Jul 2023Adenosine triphosphate (ATP) is an essential nucleotide that is normally present in both intracellular and extracellular compartments. Extracellular ATP (eATP) has a... (Review)
Review
OBJECTIVE
Adenosine triphosphate (ATP) is an essential nucleotide that is normally present in both intracellular and extracellular compartments. Extracellular ATP (eATP) has a pivotal role in both physiological and pathological processes of periodontal ligament tissues. Here, this review aimed to explore the various functions of eATP that are involved in the control of behaviours and functions of periodontal ligament cells.
METHODS
To identify the included publications for review, the articles were searched in PubMed (MEDLINE) and SCOPUS with the keywords of adenosine triphosphate and periodontal ligament cells. Thirteen publications were used as the main publications for discussion in the present review.
RESULTS
eATP has been implicated as a potent stimulator for inflammation initiation in periodontal tissues. It also plays a role in proliferation, differentiation, remodelling, and immunosuppressive functions of periodontal ligament cells. Yet, eATP has diverse functions in regulating periodontal tissue homeostasis and regeneration.
CONCLUSION
eATP may provide a new prospect for periodontal tissue healing as well as treatment of periodontal disease especially periodontitis. It may be utilized as a useful therapeutic tool for future periodontal regeneration therapy.
PubMed: 37422449
DOI: 10.1038/s41405-023-00147-7 -
Frontiers in Public Health 2023Type 2 diabetes mellitus (T2DM) accelerates the progression of periodontitis through diverse pathways. Abnormal immune responses, excessive activation of inflammation,... (Review)
Review
Type 2 diabetes mellitus (T2DM) accelerates the progression of periodontitis through diverse pathways. Abnormal immune responses, excessive activation of inflammation, increased levels of advanced glycation end products, and oxidative stress have defined roles in the pathophysiological process of T2DM-associated periodontitis. Furthermore, in the periodontium of diabetic individuals, there are high levels of advanced glycation end-products and glucose. Meanwhile, progress in microbiomics has revealed that dysbacteriosis caused by T2DM also contributes to the progression of periodontitis. , owing to its fine-tuning function in the local microbiota, has sparked tremendous interest in this field. Accumulating research on has detailed its beneficial role in both diabetes and oral diseases. In this study, we summarize the newly discovered mechanisms underlying -mediated improvement of T2DM-associated periodontitis and propose the application of in the clinic.
Topics: Humans; Diabetes Mellitus, Type 2; Periodontitis; Glucose
PubMed: 38098816
DOI: 10.3389/fpubh.2023.1248518