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Frontiers in Immunology 2021A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other... (Review)
Review
A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other sources of tissues, e.g. bone marrow, adipose or umbilical cord, GMSCs also possess multipotent differentiation capacities and potent immunomodulatory effects on both innate and adaptive immune cells through the secretion of various types of bioactive factors with immunosuppressive and anti-inflammatory functions. Uniquely, GMSCs are highly proliferative and have the propensity to differentiate into neural cell lineages due to the neural crest-origin. These properties have endowed GMSCs with potent regenerative and therapeutic potentials in various preclinical models of human disorders, particularly, some inflammatory and autoimmune diseases, skin diseases, oral and maxillofacial disorders, and peripheral nerve injuries. All types of cells release extracellular vesicles (EVs), including exosomes, that play critical roles in cell-cell communication through their cargos containing a variety of bioactive molecules, such as proteins, nucleic acids, and lipids. Like EVs released by other sources of MSCs, GMSC-derived EVs have been shown to possess similar biological functions and therapeutic effects on several preclinical diseases models as GMSCs, thus representing a promising cell-free platform for regenerative therapy. Taken together, due to the easily accessibility and less morbidity of harvesting gingival tissues as well as the potent immunomodulatory and anti-inflammatory functions, GMSCs represent a unique source of MSCs of a neural crest-origin for potential application in tissue engineering and regenerative therapy.
Topics: Cell Communication; Cell Differentiation; Cells, Cultured; Gingiva; Humans; Immunomodulation; Mesenchymal Stem Cells; Regenerative Medicine; Tissue Engineering
PubMed: 33936109
DOI: 10.3389/fimmu.2021.667221 -
Proceedings of the National Academy of... Jul 2021Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption...
Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption of this homeostatic host-bacteria relationship occurs during experimental gingivitis studies where it has been clearly established that increases in the bacterial burden increase gingival inflammation. Here, we show that experimental gingivitis resulted in three unique clinical inflammatory phenotypes (high, low, and slow) and reveal that interleukin-1β, a reported major gingivitis-associated inflammatory mediator, was not associated with clinical gingival inflammation in the slow response group. In addition, significantly higher levels of spp. were also unique to this group. The low clinical response group was characterized by low concentrations of host mediators, despite similar bacterial accumulation and compositional characteristics as the high clinical response group. Neutrophil and bone activation modulators were down-regulated in all response groups, revealing novel tissue and bone protective responses during gingival inflammation. These alterations in chemokine and microbial composition responses during experimental gingivitis reveal a previously uncharacterized variation in the human host response to a disruption in gingival homeostasis. Understanding this human variation in gingival inflammation may facilitate the identification of periodontitis-susceptible individuals. Overall, this study underscores the variability in host responses in the human population arising from variations in host immune profiles (low responders) and microbial community maturation (slow responders) that may impact clinical outcomes in terms of destructive inflammation.
Topics: Adolescent; Adult; Bone and Bones; Chemokines; Gingiva; Gingivitis; Homeostasis; Humans; Inflammation; Phylogeny; Time Factors; Young Adult
PubMed: 34193520
DOI: 10.1073/pnas.2012578118 -
Clinical Oral Implants Research Sep 2009The aim of the present review was to systematically assess the dental literature in terms of soft tissue grafting techniques. The focused question was: is one method... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of the present review was to systematically assess the dental literature in terms of soft tissue grafting techniques. The focused question was: is one method superior over others for augmentation and stability of the augmented soft tissue in terms of increasing the width of keratinized tissue (part 1) and gain in soft tissue volume (part 2).
METHODS
A Medline search was performed for human studies focusing on augmentation of keratinized tissue and/or soft tissue volume, and complemented by additional hand searching. Relevant studies were identified and statistical results were reported for meta-analyses including the test minus control weighted mean differences with 95% confidence intervals, the I-squared statistic for tests of heterogeneity, and the number of significant studies.
RESULTS
Twenty-five (part 1) and three (part 2) studies met the inclusion criteria; 14 studies (part 1) were eligible for comparison using meta-analyses. An apically positioned flap/vestibuloplasty (APF/V) procedure resulted in a statistically significantly greater gain in keratinized tissue than untreated controls. APF/V plus autogenous tissue revealed statistically significantly more attached gingiva compared with untreated controls and a borderline statistical significance compared with APF/V plus allogenic tissue. Statistically significantly more shrinkage was observed for the APF/V plus allogenic graft compared with the APF/V plus autogenous tissue. Patient-centered outcomes did not reveal any of the treatment methods to be superior regarding postoperative complications. The three studies reporting on soft tissue volume augmentation could not be compared due to lack of homogeneity. The use of subepithelial connective tissue grafts (SCTGs) resulted in statistically significantly more soft tissue volume gain compared with free gingival grafts (FGGs).
CONCLUSIONS
APF/V is a successful treatment concept to increase the width of keratinized tissue or attached gingiva around teeth. The addition of autogenous tissue statistically significantly increases the width of attached gingiva. For soft tissue volume augmentation, only limited data are available favoring SCTGs over FGG.
Topics: Collagen; Connective Tissue; Gingiva; Gingivoplasty; Humans; Keratins; Skin, Artificial; Vestibuloplasty
PubMed: 19663961
DOI: 10.1111/j.1600-0501.2009.01784.x -
Periodontology 2000 Feb 2017The key to achieving pleasing esthetics in implant dentistry is a thorough understanding of the biological processes driving dimensional bone and soft tissue alterations... (Review)
Review
The key to achieving pleasing esthetics in implant dentistry is a thorough understanding of the biological processes driving dimensional bone and soft tissue alterations post-extraction. The aim of the present report is first to characterize the extent of bone and soft tissue changes post-extraction and second to identify potential factors influencing tissue preservation in order to facilitate successful treatment outcomes. The facial bone wall thickness has been identified as the most critical factor influencing bone resorption and can be used as a prognostic tool in order to identify sites at risk for future facial bone loss subsequent to tooth extraction. Clinical studies indicated that thin bone wall phenotypes exhibiting a facial bone wall thickness of 1 mm or less revealed progressive bone resorption with a vertical loss of 7.5 mm, whereas thick bone wall phenotypes showed only minor bone resorption with a vertical loss of 1.1 mm. This is in contrast to the dimensional soft tissue alterations. Thin bone wall phenotypes revealed a spontaneous soft tissue thickening after flapless extraction by a factor of seven, whereas thick bone wall phenotypes showed no significant changes in the soft tissue dimensions after 8 weeks of healing. In sites exhibiting a limited bone resorption rate, immediate implant placement may be considered. If such ideal conditions are not present, other timing protocols are recommended to achieve predictable and pleasing esthetics. Socket preservation techniques for ridge preservation utilizing different biomaterials and/or barrier membranes often result in a better maintenance of tissue volumes, although the inevitable biological process of post-extraction bone resorption and bone modeling cannot be arrested. In summary, the knowledge of the biological events driving dimensional tissue alterations post-extraction should be integrated into the comprehensive treatment plan in order to limit tissue loss and to maximize esthetic outcomes.
Topics: Alveolar Bone Loss; Animals; Bone Remodeling; Dental Implantation, Endosseous; Dental Implants; Esthetics, Dental; Gingiva; Humans; Phenotype; Tooth Extraction; Tooth Socket
PubMed: 28000281
DOI: 10.1111/prd.12167 -
European Cells & Materials Aug 2019Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching... (Review)
Review
Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching the underlying soft tissues and bone, which in turn can lead to inflammation and subsequent bone resorption. The present review investigated oral wound closure and the role of micro-environment, saliva, crevicular fluid and microbiota in wound healing. The importance of the junctional epithelium (peri-implant epithelium) attachment to the abutment surface was investigated. Current research focuses on macro-design, surface-topography, surface-chemistry, materials, coatings and wettability to enhance attachment, since these optimised surface properties are expected to promote keratinocyte attachment and spreading through hemi-desmosome formation. Detailed studies describing the extent of junctional epithelium attachment - e.g. barrier function, hemi-desmosomes, epithelium quality, composition of the external basement membrane or ability of the epithelium to resist microbial penetration and colonisation - are not yet reported in animals due to ethical considerations, scalability, expense, technical challenges and limited availability of antibodies. In vitro studies generally include relatively simple 2D culture models, which lack the complexity required to draw relevant conclusions. Additionally, human organotypic 3D mucosa models are being developed. The present review concluded that more research using these organotypic mucosa models may identify relevant parameters involved in soft-tissue-abutment interactions, which could be used to study different macro-shapes and surface modifications. Such studies would bridge the gap between clinical, animal and traditional in vitro cell culture studies supporting development of abutments aiming at improved clinical performance.
Topics: Animals; Cell Adhesion; Dental Abutments; Epithelial Cells; Gingiva; Humans; Wound Healing
PubMed: 31410840
DOI: 10.22203/eCM.v038a06 -
Medicina Oral, Patologia Oral Y Cirugia... Jan 2011Gummy smile constitutes a relatively frequent aesthetic alteration characterized by excessive exhibition of the gums during smiling movements of the upper lip. It is the... (Review)
Review
Gummy smile constitutes a relatively frequent aesthetic alteration characterized by excessive exhibition of the gums during smiling movements of the upper lip. It is the result of an inadequate relation between the lower edge of the upper lip, the positioning of the anterosuperior teeth, the location of the upper jaw, and the gingival margin position with respect to the dental crown. Altered Passive Eruption (APE) is a clinical situation produced by excessive gum overlapping over the enamel limits, resulting in a short clinical crown appearance, that gives the sensation of hidden teeth. The term itself suggests the causal mechanism, i.e., failure in the passive phase of dental eruption, though there is no scientific evidence to support this. While there are some authors who consider APE to be a risk situation for periodontal health, its clearest clinical implication refers to oral esthetics. APE is a factor that frequently contributes to the presence of a gummy or gingival smile, and it can easily be corrected by periodontal surgery. Nevertheless, it is essential to establish a correct differential diagnosis and good treatment plan. A literature review is presented of the dental eruption process, etiological hypotheses of APE, its morphologic classification, and its clinical relevance.
Topics: Gingiva; Humans; Tooth Eruption
PubMed: 20711147
DOI: 10.4317/medoral.16.e100 -
The International Journal of... Apr 2022Unlike other non-lymphoid tissues monocytes comprise a large proportion of mononuclear phagocytes present within the gingiva. Their functions and fate remain poorly... (Review)
Review
Unlike other non-lymphoid tissues monocytes comprise a large proportion of mononuclear phagocytes present within the gingiva. Their functions and fate remain poorly understood. The oral mucosa faces challenges common to all barrier surfaces, including constant exposure to antigens and the resident commensal bacteria, but also experiences ongoing mechanical damage from mastication. Gingiva monocytes may therefore possess both myeloid functions observed at other barrier sites, such as hypo-responsiveness to bacterial stimulation, and distinctive functions tailored by their unique environment. In this review, we discuss the establishment and function of monocytes and macrophages at several mucosal tissues, and posit potential functions of monocytes within the gingiva tissue.
Topics: Bacteria; Gingiva; Macrophages; Monocytes
PubMed: 35276370
DOI: 10.1016/j.biocel.2022.106194 -
Drug Design, Development and Therapy 2020Periodontitis is a major chronic oral disease that is accelerated by activation of the NLRP3 inflammasome and the resulting pyroptosis. According to recent studies,...
PURPOSE
Periodontitis is a major chronic oral disease that is accelerated by activation of the NLRP3 inflammasome and the resulting pyroptosis. According to recent studies, active vitamin D and its analogs have been reported to have great anti-inflammatory effects. However, the anti-inflammatory mechanism of a newly found vitamin D analog, eldecalcitol (ED-71), is still unclear. This study investigates whether ED-71 could protect human gingival fibroblasts (HGFs) from LPS-induced pyroptosis and, if so, determine its underlying mechanism.
METHODS
After HGFs were treated with LPS alone or with LPS and ED-71, their viability was measured by CCK8 assay. The degrees of inflammation and pyroptosis were measured via LDH assay, HO assay, fluorescent staining, flow cytometry, and Western blots. Intracellular ROS, Hoechst 33,342, and PI stains were assessed with a fluorescence microscope. ROS inhibitor NAC, NLRP3 inhibitor MCC950, and Nrf2 inhibitor ML385 were added to further clarify the mechanism.
RESULTS
LPS induced cytotoxicity in HGFs, as shown by CCK8 assay. LPS also increased intracellular ROS, HO levels, release of LDH, and expression of the pyroptosis-related proteins NLRP3, caspase-1, and IL-1β. NAC and MCC950 reduced LPS-induced NLRP3, caspase-1, and IL-1β. Pretreatment with ED-71 effectively inhibited the LPS-induced pyroptosis and was associated with activation of the Nrf2/HO-1 signaling pathway. This beneficial effect of ED-71 was suppressed by ML385.
CONCLUSION
This study demonstrates the therapeutic effect of ED-71 on LPS-induced NLRP3 inflammasome-dependent pyroptosis in HGFs and further reveals that ED-71 can inhibit pyroptosis by activating the Nrf2/HO-1 pathway. Our results thus suggest that ED-71 is a potential candidate for the treatment of periodontitis.
Topics: Cell Survival; Cells, Cultured; Fibroblasts; Gingiva; Heme Oxygenase-1; Humans; Inflammasomes; Lipopolysaccharides; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Signal Transduction; Vitamin D
PubMed: 33223823
DOI: 10.2147/DDDT.S269223 -
Cells Oct 2022Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many... (Review)
Review
Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many inflammatory cytokines secreted by immune or tissue cells, such as interleukin-6. In contrast, gingival overgrowth develops as a side effect of specific drugs, such as immunosuppressants, anticonvulsants, and calcium channel blockers. Human gingival fibroblasts (HGFs) are the most abundant cells in gingival connective tissue, and human periodontal ligament fibroblasts (HPLFs) are located between the teeth and alveolar bone. HGFs and HPLFs are both crucial for the remodeling and homeostasis of periodontal tissue, and their roles in the pathogenesis of periodontal diseases have been examined for 25 years. Various responses by HGFs or HPLFs contribute to the progression of periodontal diseases. This review summarizes the biological effects of HGFs and HPLFs on the pathogenesis of periodontal diseases.
Topics: Humans; Gingiva; Fibroblasts; Periodontal Ligament; Periodontitis; Gingival Overgrowth
PubMed: 36359741
DOI: 10.3390/cells11213345 -
Frontiers in Immunology 2021The subgingival biofilm attached to tooth surfaces triggers and maintains periodontitis. Previously, late-onset periodontitis has been considered a consequence of... (Review)
Review
The subgingival biofilm attached to tooth surfaces triggers and maintains periodontitis. Previously, late-onset periodontitis has been considered a consequence of dysbiosis and a resultant polymicrobial disruption of host homeostasis. However, a multitude of studies did not show "healthy" oral microbiota pattern, but a high diversity depending on culture, diets, regional differences, age, social state etc. These findings relativise the aetiological role of the dysbiosis in periodontitis. Furthermore, many late-onset periodontitis traits cannot be explained by dysbiosis; e.g. age-relatedness, attenuation by anti-ageing therapy, neutrophil hyper-responsiveness, and microbiota shifting by dysregulated immunity, yet point to the crucial role of dysregulated immunity and neutrophils in particular. Furthermore, patients with neutropenia and neutrophil defects inevitably develop early-onset periodontitis. Intra-gingivally injecting lipopolysaccharide (LPS) alone causes an exaggerated neutrophil response sufficient to precipitate experimental periodontitis. Vice versa to the surplus of LPS, the increased neutrophil responsiveness characteristic for late-onset periodontitis can effectuate gingiva damage likewise. The exaggerated neutrophil extracellular trap (NET) response in late-onset periodontitis is blameable for damage of gingival barrier, its penetration by bacteria and pathogen-associated molecular patterns (PAMPs) as well as stimulation of Th17 cells, resulting in further neutrophil activation. This identifies the dysregulated immunity as the main contributor to periodontal disease.
Topics: Animals; Bacteria; Biofilms; Dysbiosis; Extracellular Traps; Gingiva; Humans; Inflammation Mediators; Neutrophil Activation; Neutrophils; Pathogen-Associated Molecular Pattern Molecules; Periodontal Pocket; Periodontitis; Signal Transduction
PubMed: 34899756
DOI: 10.3389/fimmu.2021.788766