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Journal of Dental Research Mar 2024Periodontal mesenchymal stem cells (MSCs) play a crucial role in maintaining periodontium homeostasis and in tissue repair. However, little is known about how...
Periodontal mesenchymal stem cells (MSCs) play a crucial role in maintaining periodontium homeostasis and in tissue repair. However, little is known about how periodontal MSCs in vivo respond under periodontal disease conditions, posing a challenge for periodontium tissue regeneration. In this study, Gli1 was used as a periodontal MSC marker and combined with a Gli1-cre ERT2 mouse model for lineage tracing to investigate periodontal MSC fate in an induced periodontitis model. Our findings show significant changes in the number and contribution of Gli1 MSCs within the inflamed periodontium. The number of Gli1 MSCs that contributed to periodontal ligament homeostasis decreased in the periodontitis-induced teeth. While the proliferation of Gli1 MSCs had no significant difference between the periodontitis and the control groups, more Gli1 MSCs underwent apoptosis in diseased teeth. In addition, the number of Gli1 MSCs for osteogenic differentiation decreased during the progression of periodontitis. Following tooth extraction, the contribution of Gli1 MSCs to the tooth socket repair was significantly reduced in the periodontitis-induced teeth. Collectively, these findings indicate that the function of Gli1 MSCs in periodontitis was compromised, including reduced contribution to periodontium homeostasis and impaired injury response.
Topics: Mice; Animals; Zinc Finger Protein GLI1; Osteogenesis; Periodontitis; Periodontium; Mesenchymal Stem Cells; Periodontal Ligament
PubMed: 38284236
DOI: 10.1177/00220345231220915 -
Bioactive Materials Mar 2024Type 2 diabetes mellitus (T2DM) exacerbates irreversible bone loss in periodontitis, but the mechanism of impaired bone regeneration caused by the abnormal metabolic...
Type 2 diabetes mellitus (T2DM) exacerbates irreversible bone loss in periodontitis, but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear. Exosomes are regarded as the critical mediator in diabetic impairment of regeneration via organ or tissue communication. Here, we find that abnormally elevated exosomes derived from metabolically impaired liver in T2DM are significantly enriched in the periodontal region and induced pyroptosis of periodontal ligament cells (PDLCs). Mechanistically, fatty acid synthase (Fasn), the main differentially expressed molecule in diabetic exosomes results in ectopic fatty acid synthesis in PDLCs and activates the cleavage of gasdermin D. Depletion of liver Fasn effectively mitigates pyroptosis of PDLCs and alleviates bone loss. Our findings elucidate the mechanism of exacerbated bone loss in diabetic periodontitis and reveal the exosome-mediated organ communication in the "liver-bone" axis, which shed light on the prevention and treatment of diabetic bone disorders in the future.
PubMed: 38024229
DOI: 10.1016/j.bioactmat.2023.10.022 -
Journal of Clinical Periodontology Sep 2023Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis...
AIM
Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis inhibitors in attenuating periodontitis.
MATERIALS AND METHODS
The Gene Expression Omnibus (GEO) dataset GSE164241 was re-analysed to identify the role of necroptosis in periodontitis. Gingival specimens from healthy subjects or periodontitis patients were collected to evaluate the expression level of necroptosis-associated proteins. The therapeutic effect of necroptosis inhibitors on periodontitis was assessed in vivo and in vitro. Moreover, Transwell assays and Western blotting and siRNA transfection were used to identify the effects of necroptotic human gingival fibroblasts (hGFs) on THP-1 macrophages.
RESULTS
Re-analysis revealed that gingival fibroblasts (GFs) in periodontitis gingiva showed the highest area under the curve score of necroptosis. Elevated levels of necroptosis-associated proteins were identified in GFs in periodontitis gingiva collected from patients and mice. In ligature-induced periodontitis mice, local administration of receptor interacting protein kinase 3(RIPK3) inhibitor GSK'872 or sh-mixed-lineage kinase domain-like pseudokinase (Mlkl) markedly abrogated necroptosis and rescued periodontitis. Analogously, necroptosis inhibitors alleviated the inflammatory response and release of damage-associated molecular patterns in lipopolysaccharide- or LAZ (LPS + AZD'5582 + z-VAD-fmk, necroptosis inducer)-induced GFs and then reduced THP-1 cell migration and M1 polarization.
CONCLUSIONS
Necroptosis in GFs aggravated gingival inflammation and alveolar bone loss. Necroptosis inhibitors attenuate this process by modulating THP-1 macrophage migration and polarization. This study offers novel insights into the pathogenesis and potential therapeutic targets of periodontitis.
Topics: Humans; Mice; Animals; Protein Kinases; Gingiva; Necroptosis; Periodontitis; Fibroblasts; Gingivitis; Receptor-Interacting Protein Serine-Threonine Kinases
PubMed: 37366309
DOI: 10.1111/jcpe.13841 -
Pharmaceutics Dec 2023Periodontitis is a global, multifaceted, chronic inflammatory disease caused by bacterial microorganisms and an exaggerated host immune response that not only leads to... (Review)
Review
Periodontitis is a global, multifaceted, chronic inflammatory disease caused by bacterial microorganisms and an exaggerated host immune response that not only leads to the destruction of the periodontal apparatus but may also aggravate or promote the development of other systemic diseases. The periodontium is composed of four different tissues (alveolar bone, cementum, gingiva, and periodontal ligament) and various non-surgical and surgical therapies have been used to restore its normal function. However, due to the etiology of the disease and the heterogeneous nature of the periodontium components, complete regeneration is still a challenge. In this context, guided tissue/bone regeneration strategies in the field of tissue engineering and regenerative medicine have gained more and more interest, having as a goal the complete restoration of the periodontium and its functions. In particular, the use of electrospun nanofibrous scaffolds has emerged as an effective strategy to achieve this goal due to their ability to mimic the extracellular matrix and simultaneously exert antimicrobial, anti-inflammatory and regenerative activities. This review provides an overview of periodontal regeneration using electrospun membranes, highlighting the use of these nanofibrous scaffolds as delivery systems for bioactive molecules and drugs and their functionalization to promote periodontal regeneration.
PubMed: 38140066
DOI: 10.3390/pharmaceutics15122725 -
Cells Aug 2023Adult human gingival fibroblasts (HGFs), the most abundant cells in the oral cavity, are essential for maintaining oral homeostasis. Compared with other tissues, adult... (Review)
Review
Adult human gingival fibroblasts (HGFs), the most abundant cells in the oral cavity, are essential for maintaining oral homeostasis. Compared with other tissues, adult oral mucosal wounds heal regeneratively, without scarring. Relative to fibroblasts from other locations, HGFs are relatively refractory to myofibroblast differentiation, immunomodulatory, highly regenerative, readily obtained via minimally invasive procedures, easily and rapidly expanded in vitro, and highly responsive to growth factors and cytokines. Consequently, HGFs might be a superior, yet perhaps underappreciated, source of adult mesenchymal progenitor cells to use in tissue engineering and regeneration applications, including the treatment of fibrotic auto-immune connective tissue diseases such as scleroderma. Herein, we highlight in vitro and translational studies that have investigated the regenerative and differentiation potential of HGFs, with the objective of outlining current limitations and inspiring future research that could facilitate translating the regenerative potential of HGFs into the clinic.
Topics: Adult; Humans; Regenerative Medicine; Gingiva; Fibroblasts; Mouth; Mouth Mucosa
PubMed: 37626831
DOI: 10.3390/cells12162021 -
Dental and Medical Problems 2023Diet and eating habits significantly affect health and quality of life. Various diets and food eliminations can lead to nutritional deficiencies and malnutrition. This... (Review)
Review
Diet and eating habits significantly affect health and quality of life. Various diets and food eliminations can lead to nutritional deficiencies and malnutrition. This article discusses the relationship between nutrition, nutritional deficiencies, and the condition of the periodontium and oral mucosa. An analysis of PubMed materials was conducted to assess the impact of nutrition on the condition of the oral mucosa and periodontium. We also considered dietary habits such as vegetarianism, the ketogenic diet, the Paleo diet, the Mediterranean diet, the Western diet, and intermittent fasting. Vitamin deficiencies, both watersoluble and fat-soluble, as well as macroand microelements, can manifest in the oral cavity, among others, as gingivitis and bleeding, recurrent aphthous stomatitis, enamel hypomineralization, cheilitis, angular cheilitis, halitosis, glossitis, lingual papillae atrophy, and stomatitis. Malnutrition does not cause periodontal disease, but it increases the risk of its occurrence and accelerates disease progression. Inadequate nutrition, combined with other predisposing factors, may contribute to an increased risk of oral cancer and the development of leukoplakia.
Topics: Humans; Mouth Mucosa; Cheilitis; Quality of Life; Periodontium; Malnutrition
PubMed: 38133993
DOI: 10.17219/dmp/156466 -
Cureus Oct 2023The aim of this review was to evaluate the relationship between periodontal disease (PD) and the onset and progression of Alzheimer's disease (AD) and to determine... (Review)
Review
The aim of this review was to evaluate the relationship between periodontal disease (PD) and the onset and progression of Alzheimer's disease (AD) and to determine whether patients with PD would be at greater risk of developing AD compared to periodontally healthy subjects. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search for cross-sectional, cohort, or case-control studies was conducted on five databases (PubMed, ScienceDirect, EBSCO, Web of Science, and Scopus). No restrictions were applied to the language and year of publication. Exposure was PD, and the outcome of interest was the onset and/or progression of AD. The risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) designed for non-randomized studies. Six studies fulfilling the selection criteria were included in this systematic review. Four of the studies were of cohort design and two were of case-control design. All except one showed a significant association between PD and the risk of AD onset and progression. According to the NOS bias risk assessment, three studies were found to be of good quality, and three other cohort studies were of low quality. Data from this systematic review indicate that patients with PD present a significantly higher risk of AD compared to individuals with healthy periodontium. However, results should be interpreted with caution given the methodological limitations found. For future research, powerful and comparable epidemiological studies are needed to evaluate the relationship between PD and AD.
PubMed: 37916259
DOI: 10.7759/cureus.46311 -
Frontiers in Endocrinology 2023Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of... (Review)
Review
Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.
Topics: Humans; Diabetes Mellitus; Periodontitis; Hyperglycemia; Risk Factors; Bone Resorption
PubMed: 37664859
DOI: 10.3389/fendo.2023.1192625 -
Cell and Tissue Research Jul 2023Stem cells derived from dental/odontogenic tissue have the property of multiple differentiation and are prospective in tooth regenerative medicine and cellular and... (Review)
Review
Stem cells derived from dental/odontogenic tissue have the property of multiple differentiation and are prospective in tooth regenerative medicine and cellular and molecular studies. However, in the face of cellular senescence soon in vitro, the proliferation ability of the cells is limited, so studies are hindered to some extent. Fortunately, immortalization strategies are expected to solve the above issues. Cellular immortalization is that cells are immortalized by introducing oncogenes, human telomerase reverse transcriptase genes (hTERT), or miscellaneous immortalization genes to get unlimited proliferation. At present, a variety of immortalized stem cells from dental/odontogenic tissue has been successfully generated, such as dental pulp stem cells (DPSCs), periodontal ligament cells (PDLs), stem cells from human exfoliated deciduous teeth (SHEDs), dental papilla cells (DPCs), and tooth germ mesenchymal cells (TGMCs). This review summarized establishment and applications of immortalized stem cells from dental/odontogenic tissues and then discussed the advantages and challenges of immortalization.
Topics: Humans; Prospective Studies; Tooth; Cell Line; Periodontal Ligament; Mesenchymal Stem Cells; Cell Differentiation; Dental Pulp; Cell Proliferation
PubMed: 37039940
DOI: 10.1007/s00441-023-03767-5 -
Journal of Dental Research Nov 2023Physiologically, teeth and periodontal tissues are exposed to occlusal forces throughout their lifetime. Following occlusal unloading, unbalanced bone remodeling...
Physiologically, teeth and periodontal tissues are exposed to occlusal forces throughout their lifetime. Following occlusal unloading, unbalanced bone remodeling manifests as a net alveolar bone (AB) loss. This phenomenon is termed (ABDO), the underlying mechanism of which remains unclear. Type H vessels, a novel capillary subtype tightly coupled with osteogenesis, reportedly have a role in skeletal remodeling; however, their role in ABDO is not well studied. In the present study, we aimed to explore the pathogenesis of and therapies for ABDO. The study revealed that type H endothelium highly positive for CD31 and endomucin was identified in the periodontal ligament (PDL) but rarely in the AB of the mice. In hypofunctional PDL, the density of type H vasculature and coupled osterix (OSX) osteoprogenitors declined significantly. In addition, the angiogenic factor Slit guidance ligand 3 (SLIT3) was downregulated in the disused PDL, and periodontal injection of the recombinant SLIT3 protein partially ameliorated type H vessel dysfunction and AB loss in ABDO mice. With regard to the molecular mechanism, a mechanosensory signaling circuit, PIEZO1/Ca/HIF-1α/SLIT3, was validated by applying cyclic compression to 3-dimensional-cultured PDL cells using the Flexcell FX-5000 compression system. In summary, PDL plays a pivotal role in mechanotransduction by translating physical forces into the intracellular signaling axis PIEZO1/Ca/HIF-1α/SLIT3, which promotes type H angiogenesis and OSX cell-related osteogenensis, thereby contributing to AB homeostasis. Our findings advance the understanding of PDL in AB disorders. Further therapies targeting SLIT3 may provide new insights into preventing bone loss in ABDO.
Topics: Mice; Animals; Bite Force; Mechanotransduction, Cellular; Tooth; Periodontal Ligament; Alveolar Bone Loss; Homeostasis
PubMed: 37786932
DOI: 10.1177/00220345231191745