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Biomolecules Sep 2023Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune...
Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed.
Topics: Humans; Matrix Metalloproteinase 2; Periodontal Ligament; Interleukin-17; Osteogenesis; Doxycycline; Periodontitis; Stem Cells; Cell Differentiation; Cells, Cultured
PubMed: 37892119
DOI: 10.3390/biom13101437 -
Immunity, Inflammation and Disease Dec 2022Periodontitis is a common oral inflammatory disease, and lipopolysaccharide (LPS) is a key risk factor in periodontitis pathology. Here, we used LPS-induced periodontal...
BACKGROUND
Periodontitis is a common oral inflammatory disease, and lipopolysaccharide (LPS) is a key risk factor in periodontitis pathology. Here, we used LPS-induced periodontal ligament cells (PDLCs) to explore the molecular mechanism of periodontitis.
METHODS
Cell viability, proliferation, and apoptosis were analyzed by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine (EDU), and flow cytometry assays, respectively. Apart from that, their targeting relationship was validated using dual-luciferase reporter and RNA-pull down.
RESULTS
Circular RNA_0138960 (circ_0138960) was notably upregulated in periodontitis sufferers (p < .001) and LPS-disposed PDLCs (p < .05). LPS exposure dampened PDLC proliferation, and promoted apoptosis and inflammation (p < .05). Circ_0138960 acted as a microRNA sponge for miR-518a-5p to affect histone deacetylase 6 (HDAC6) expression. Circ_0138960 absence-mediated protective effects in LPS-induced PDLCs were largely abrogated via silencing miR-518a-5p or HDAC6 overexpression (p < .05).
CONCLUSION
Circ_0138960 promoted LPS-induced dysfunction in PDLCs by targeting miR-518a-5p/HDAC6 axis, which provided novel potential therapeutic targets for periodontitis.
Topics: Humans; Periodontal Ligament; Lipopolysaccharides; Inflammation; Cell Survival; MicroRNAs
PubMed: 36444635
DOI: 10.1002/iid3.732 -
International Journal of Nanomedicine 2023Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes...
INTRODUCTION
Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis.
METHODS
Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis.
RESULTS
PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface.
CONCLUSION
Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.
Topics: Animals; Mice; Alveolar Bone Loss; Exosomes; Periodontal Ligament; Stem Cells; Disease Models, Animal; Glucose; MicroRNAs
PubMed: 37746047
DOI: 10.2147/IJN.S409664 -
Molecules (Basel, Switzerland) Jan 2023The success of a prosthetic treatment is closely related to the periodontal health of the individual. The aim of this article was to review and present the importance of... (Review)
Review
The success of a prosthetic treatment is closely related to the periodontal health of the individual. The aim of this article was to review and present the importance of prosthetic restorative materials on the condition of the periodontium, the changes that occur in the composition of the subgingival microbiota and the levels of inflammatory markers in gingival crevicular fluid. Articles on the influence of different prosthetic restorative materials on subgingival microbiota and proinflammatory cytokines were searched for using the keywords "prosthetic biomaterials", "fixed prosthesis", "periodontal health", "subgingival microbiota", "periodontal biomarkers" and "gingival crevicular fluid" in PubMed/Medline, Science Direct, Scopus and Google Scholar. The type of material used for prosthesis fabrication together with poor marginal and internal fit can result in changes in the composition of the subgingival microbiota, as well as increased accumulation and retention of dentobacterial plaque, thus favoring the development of periodontal disease and prosthetic treatment failure. Biological markers have helped to understand the inflammatory response of different prosthetic materials on periodontal tissues with the main purpose of improving their clinical application in patients who need them. Metal-free ceramic prostheses induce a lower inflammatory response regardless of the fabrication method; however, the use of CAD/CAM systems is recommended for their fabrication. In addition, it is presumed that metal-ceramic prostheses cause changes in the composition of the subgingival microbiota producing a more dysbiotic biofilm with a higher prevalence of periodontopathogenic bacteria, which may further favor periodontal deterioration.
Topics: Humans; Periodontium; Periodontal Ligament; Gingival Crevicular Fluid; Cytokines; Microbiota; Biomarkers
PubMed: 36770741
DOI: 10.3390/molecules28031075 -
Stem Cell Research & Therapy May 2020Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem... (Review)
Review
BACKGROUND
Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem cells. Recently, dental tissue-derived cells have been used clinically due to their great potential, easy accessibility, and ability to be obtained via methods with low invasiveness. The aim of this study is to systematically assess the clinical effectiveness of dental cell-mediated therapies compared to current evidence-based methods in human patients.
METHODS
The electronic databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched up to December 2019 for clinical trials. Clinical trials with any intervention using stem cells/cells derived from dental tissue were included.
RESULTS
A total of 815 studies were identified by the electronic search, and 38 articles qualified for full-text evaluation. Finally, 20 studies (10 clinical trials using dental pulp-derived cells, 3 clinical trials using periodontal ligament-derived cells, and 7 studies using gingiva-derived cells) were included in this review. No clinical trials using dental follicle- or apical papilla-derived cells were selected in this review. Dental pulp-derived cells were used in clinical trials for bone regeneration, periodontitis, and dental pulp regeneration. All clinical trials using periodontal ligament-derived cells and gingiva-derived cells were conducted for periodontal disease treatment and gingival augmentation, respectively. Among the 20 selected studies, 16 showed clinical benefits of cell transplantation therapies. In addition, no study reported adverse events that may have been associated with cell transplantation.
CONCLUSIONS
These findings indicate that dental tissue-derived cells would be useful for cell-based regenerative medicine for various diseases.
Topics: Clinical Trials as Topic; Dental Pulp; Gingiva; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regenerative Medicine
PubMed: 32398041
DOI: 10.1186/s13287-020-01683-x -
Brazilian Dental Journal 2011In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients... (Review)
Review
In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer's disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.
Topics: Animals; Cell Differentiation; Dental Papilla; Dental Pulp; Dental Sac; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Molar, Third; Periodontal Ligament; Regeneration; Tissue Engineering; Tooth Apex; Tooth Exfoliation; Tooth, Deciduous
PubMed: 21537580
DOI: 10.1590/s0103-64402011000200001 -
Stem Cell Research & Therapy Jun 2022The damaged neuronal cells of adult mammalian lack the regenerative ability to replace the neuronal connections. Periodontal ligament stem cells (PDLSCs) are the... (Review)
Review
BACKGROUND
The damaged neuronal cells of adult mammalian lack the regenerative ability to replace the neuronal connections. Periodontal ligament stem cells (PDLSCs) are the promising source for neuroregenerative applications that can improve the injured microenvironment of the damaged neural system. They provide neuronal progenitors and neurotrophic, anti-apoptotic and anti-inflammatory factors. In this study, we aimed to comprehensively explore the various neuronal differentiation potentials of PDLSCs for application in neural regeneration therapy.
MAIN TEXT
PDLSCs have superior potential to differentiate into various neural-like cells through a dedifferentiation stage followed by differentiation process without need for cell division. Diverse combination of nutritional factors can be used to induce the PDLSCs toward neural lineage. PDLSCs when coupled with biomaterials could have significant implications for neural tissue repair. PDLSCs can be a new clinical research target for Alzheimer's disease treatment, multiple sclerosis and cerebral ischemia. Moreover, PDLSCs have beneficial effects on retinal ganglion cell regeneration and photoreceptor survival. PDLSCs can be a great source for the repair of injured peripheral nerve through the expression of several neural growth factors and differentiation into Schwann cells.
CONCLUSION
In conclusion, these cells are an appealing source for utilizing in clinical treatment of the neuropathological disorders. Although significant in vitro and in vivo investigations were carried out in order for neural differentiation evaluation of these cells into diverse types of neurons, more preclinical and clinical studies are needed to elucidate their therapeutic potential for neural diseases.
Topics: Animals; Cell Differentiation; Cells, Cultured; Mammals; Nerve Regeneration; Osteogenesis; Periodontal Ligament; Stem Cells
PubMed: 35729595
DOI: 10.1186/s13287-022-02942-9 -
European Journal of Oral Sciences Feb 2021Scaling and root planning is a key element in the mechanical therapy used for the eradication of biofilm, which is the major etiological factor for periodontitis and... (Review)
Review
Scaling and root planning is a key element in the mechanical therapy used for the eradication of biofilm, which is the major etiological factor for periodontitis and peri-implantitis. However, periodontitis is also a host mediated disease, therefore, removal of the biofilm without adjunctive therapy may not achieve the desired clinical outcome due to persistent activation of the innate and adaptive immune cells. Most recently, even the resident cells of the periodontium, including periodontal ligament fibroblasts, have been shown to produce several inflammatory factors in response to bacterial challenge. With increased understanding of the pathophysiology of periodontitis, more research is focusing on opposing excessive inflammation with specialized pro-resolving mediators (SPMs). This review article covers the major limitations of current standards of care for periodontitis and peri-implantitis, and it highlights recent advances and prospects of SPMs in the context of tissue reconstruction and regeneration. Here, we focus primarily on the role of SPMs in restoring tissue homeostasis after periodontal infection.
Topics: Dental Implants; Humans; Inflammation; Peri-Implantitis; Periodontal Ligament; Periodontitis; Periodontium
PubMed: 33565133
DOI: 10.1111/eos.12759 -
European Cells & Materials Jan 2023Periodontitis is a progressive disease that ultimately leads to bone and tooth loss. A major consequence of periodontal disease is the inability to regain lost bone in...
Periodontitis is a progressive disease that ultimately leads to bone and tooth loss. A major consequence of periodontal disease is the inability to regain lost bone in the periodontium. The importance was demonstrated of glucose-regulated protein-78 (GRP78) in the osteogenic differentiation of periodontal ligament stem cells and their potential use for regeneration of the periodontium. Previous studies have shown the relationship between GRP78 and dentine matrix protein-1 (DMP1). The importance of this receptor-ligand complex in supporting the process of osteogenesis and angiogenesis was confirmed in this study. To show the function of GRP78 in mineralised tissues, transgenic periodontal ligament stem cells (PDLSCs) were generated in which GRP78 was either overexpressed or silenced. Gene expression analysis of the cells cultured under osteogenic conditions showed an increase in key osteogenic genes with the overexpression of GRP78. RNA-Seq analysis was also performed to understand the transcriptome profile associated with genotype changes. Using the database for annotation, visualisation, and integration discovery (DAVID) for the functional enrichment analysis of differentially expressed genes, the upregulation of genes promoting osteogenesis and angiogenesis with GRP78 overexpression was demonstrated. Alizarin red staining and scanning electron microscopy analysis revealed matrix mineralisation with increased calcium deposition in GRP78 overexpressing cells. The in vivo osteogenic and angiogenic function of GRP78 was shown using a subcutaneous implantation rodent model. The results suggested that GRP78 in PDLSCs can regulate the expression of both osteogenesis and angiogenesis. Therefore, GRP78 could be considered as a therapeutic target for repair of diseased periodontium.
Topics: Cell Differentiation; Cells, Cultured; Endoplasmic Reticulum Chaperone BiP; Osteogenesis; Periodontal Ligament; Stem Cells; Neovascularization, Physiologic
PubMed: 36683528
DOI: 10.22203/eCM.v045a02 -
Bioscience Reports Jun 2018Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) remodelling enzymes involved in developmental processes, tissue remodelling and repair, inflammatory and...
Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) remodelling enzymes involved in developmental processes, tissue remodelling and repair, inflammatory and immune diseases and cancer. In a recent issue of (vol. 37, issue 6, BSR20170973), Liu and colleagues investigated the expression of MMPs such as MMP-1 (interstitial collagenase), MMP-3 (stromelysin 1) and MMP-13 (collagenase 3) in human periodontal ligament fibroblasts (hPDLFs) regulated by interleukin-12 (IL-12), a cytokine implicated in inflammatory and immune responses. They showed that IL-12 activates canonical nuclear factor-κB (NF-κB) signalling leading to increased expression of MMP-1, MMP-3 and MMP-13, and to a smaller reduction in the expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) at both mRNA and protein levels, with corresponding changes in the secreted levels of these ECM-remodelling and immune regulatory metalloproteinases. While canonical NF-κB signalling regulates these MMPs, it also interacts with additional factors to determine whether some of these MMPs are induced or downregulated, in response to IL-12. Here, we comment on the possible mechanisms of IL-12-mediated transcriptional regulation of MMPs.
Topics: Fibroblasts; Humans; Interleukin-12; Matrix Metalloproteinase 12; NF-kappa B; Periodontal Ligament
PubMed: 29555826
DOI: 10.1042/BSR20171420