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FASEB Journal : Official Publication of... Nov 2023Cementum, a constituent part of periodontal tissues, has important adaptive and reparative functions. It serves to attach the tooth to alveolar bone and acts as a...
Cementum, a constituent part of periodontal tissues, has important adaptive and reparative functions. It serves to attach the tooth to alveolar bone and acts as a barrier delimit epithelial growth and bacteria evasion. A dynamic and highly responsive cementum is essential for maintaining occlusal relationships and the integrity of the root surface. It is a thin layer of mineralized tissue mainly produced by cementoblasts. Cementoblasts are osteoblast-like cells essential for the restoration of periodontal tissues. In recent years, glucose metabolism has been found to be critical in bone remodeling and osteoblast differentiation. However, the glucose metabolism of cementoblasts remains incompletely understood. First, immunohistochemistry staining and in vivo tracing with F-fluorodeoxyglucose ( F-FDG) revealed significantly higher glucose metabolism in cementum formation. To test the bioenergetic pathways of cementoblast differentiation, we compared the bioenergetic profiles of mineralized and unmineralized cementoblasts. As a result, we observed a significant increase in the consumption of glucose and production of lactate, coupled with the higher expression of glycolysis-related genes. However, the expression of oxidative phosphorylation-related genes was downregulated. The verified results were consistent with the RNA sequencing results. Likewise, targeted energy metabolomics shows that the levels of glycolytic metabolites were significantly higher in the mineralized cementoblasts. Seahorse assays identified an increase in glycolytic flux and reduced oxygen consumption during cementoblast mineralization. Apart from that, we also found that lactate dehydrogenase A (LDHA), a key glycolysis enzyme, positively regulates the mineralization of cementoblasts. In summary, cementoblasts mainly utilized glycolysis rather than oxidative phosphorylation during the mineralization process.
Topics: Dental Cementum; Cell Differentiation; Immunohistochemistry; Lactic Acid; Glucose
PubMed: 37847512
DOI: 10.1096/fj.202300870RR -
Clinical Oral Investigations Mar 2024To investigate the oral manifestations in women of reproductive age using hormonal contraceptive methods. (Review)
Review
OBJECTIVES
To investigate the oral manifestations in women of reproductive age using hormonal contraceptive methods.
MATERIALS AND METHODS
This review is based on the PRISMA statement. A literature search incorporated observational studies from the last 21 years. An investigative question was formulated using the PICO model, studies were selected, and a quality analysis was performed using the modified STROBE guidelines. A bibliometric analysis was performed, and the data were examined.
RESULTS
Thirteen articles were included, with the majority evaluating periodontal status. Others analyzed factors such as the presence of alveolar osteitis, oral candidiasis, and salivary microbiome dysbiosis. Ten articles were deemed to have a low risk of bias.
CONCLUSIONS
Hormonal contraceptives may increase the risk of alveolar osteitis following tooth extraction and increase the presence of the Candida species in the oral cavity. They also affect the periodontium, such as the frequent development of gingivitis, but do not lead to changes in the salivary microbiome.
CLINICAL RELEVANCE
The increasing number of women using hormonal contraceptives and the knowledge that these contraceptives can produce oral cavity alterations underscore the need to evaluate the oral manifestations found in these women.
Topics: Female; Humans; Dry Socket; Contraceptives, Oral, Hormonal; Periodontium; Gingivitis; Contraception
PubMed: 38427087
DOI: 10.1007/s00784-024-05573-x -
Cellular Signalling Aug 2023Orthodontic treatment in older adults is more difficult than in younger adults, partially due to delayed osteogenesis caused by senescence of human periodontal ligament...
Orthodontic treatment in older adults is more difficult than in younger adults, partially due to delayed osteogenesis caused by senescence of human periodontal ligament stem cells (hPDLSCs). The production of brain-derived neurotrophic factor (BDNF) which regulates the differentiation and survival of stem cells decreases with age. We aimed to investigate the relationship between BDNF and hPDLSC senescence and its effects on orthodontic tooth movement (OTM). We constructed mouse OTM models using orthodontic nickel‑titanium springs and compared the responses of wild-type (WT) and BDNF mice with or without addition of exogenous BDNF. In vitro, hPDLSCs subjected to the mechanical stretch were used to simulate the cell stretch environment during OTM. We extracted periodontal ligament cells from WT and BDNF mice to evaluate their senescence-related indicators. The application of orthodontic force increased BDNF expression in the periodontium of WT mice, while the mechanical stretch increased BDNF expression in hPDLSCs. Osteogenesis-related indicators, including RUNX2 and ALP decreased and cellular senescence-related indicators such as p16, p53 and β-galactosidase increased in BDNF mice periodontium. Furthermore, periodontal ligament cells extracted from BDNF mice exhibited more senescent compared with cells from WT mice. Application of exogenous BDNF decreased the expression of senescence-related indicators in hPDLSCs by inhibiting Notch3, thereby promoting osteogenic differentiation. Periodontal injection of BDNF decreased the expression of senescence-related indicators in periodontium of aged WT mice. In conclusion, our study showed that BDNF promotes osteogenesis during OTM by alleviating hPDLSCs senescence, paving a new path for future research and clinical applications.
Topics: Animals; Humans; Mice; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cells, Cultured; Cellular Senescence; Osteogenesis; Periodontal Ligament; Stem Cells; Tooth Movement Techniques
PubMed: 37211081
DOI: 10.1016/j.cellsig.2023.110724 -
Journal of Advanced Research Jun 2024Periodontal regeneration, specifically the restoration of the cementum-periodontal ligament (PDL)-alveolar bone complex, remains a formidable challenge in the field of...
INTRODUCTION
Periodontal regeneration, specifically the restoration of the cementum-periodontal ligament (PDL)-alveolar bone complex, remains a formidable challenge in the field of regenerative dentistry. In light of periodontal development, harnessing the multi-tissue developmental capabilities of periodontal ligament cells (PDLCs) and reinitiating the periodontal developmental process hold great promise as an effective strategy to foster the regeneration of the periodontal complex.
OBJECTIVES
This study aims to delve into the potential effects of the macrophage-mediated immune microenvironment on the "developmental engineering" regeneration strategy and its underlying molecular mechanisms.
METHODS
In this study, we conducted a comprehensive examination of the periodontium developmental process in the rat mandibular first molar using histological staining. Through the induction of diverse immune microenvironments in macrophages, we evaluated their potential effects on periodontal re-development events using a cytokine array. Additionally, we investigated PDLC-mediated periodontal re-development events under these distinct immune microenvironments through transcriptome sequencing and relevant functional assays. Furthermore, the underlying molecular mechanism was also performed.
RESULTS
The activation of development-related functions in PDLCs proved challenging due to their declined activity. However, our findings suggest that modulating the macrophage immune response can effectively regulate PDLCs-mediated periodontium development-related events. The M1 type macrophage immune microenvironment was found to promote PDLC activities associated with epithelial-mesenchymal transition, fiber degradation, osteoclastogenesis, and inflammation through the Wnt, IL-17, and TNF signaling pathways. Conversely, the M2 type macrophage immune microenvironment demonstrated superiority in inducing epithelium induction, fibers formation, and mineralization performance of PDLCs by upregulating the TGFβ and PI3K-Akt signaling pathway.
CONCLUSION
The results of this study could provide some favorable theoretical bases for applying periodontal development engineering strategy in resolving the difficulties in periodontal multi-tissue regeneration.
Topics: Periodontal Ligament; Animals; Macrophages; Rats; Male; Regeneration; Cellular Microenvironment; Cells, Cultured; Rats, Sprague-Dawley; Cell Differentiation; Cytokines; Signal Transduction; Molar
PubMed: 37597747
DOI: 10.1016/j.jare.2023.08.009 -
Anatomical Record (Hoboken, N.J. : 2007) May 2024PIEZO1 and PIEZO2 are essential components of mechanogated ion channels, which are required for mechanotransduction and biological processes associated with mechanical...
PIEZO1 and PIEZO2 are essential components of mechanogated ion channels, which are required for mechanotransduction and biological processes associated with mechanical stimuli. There is evidence for the presence of PIEZO1 and PIEZO2 in teeth and periodontal ligaments, especially in cell lines and mice, but human studies are almost nonexistent. Decalcified permanent human teeth and mouse molars were processed for immunohistochemical detection of PIEZO1 and PIEZO2. Confocal laser microscopy was used to examine the co-localization of PIEZO 1 and PIEZO2 with vimentin (a marker of differentiated odontoblasts) in human teeth. In the outer layer of the human dental pulp, abundant PIEZO1- and PIEZO2-positive cells were found that had no odontoblast morphology and were vimentin-negative. Based on their morphology, location, and the absence of vimentin positivity, they were identified as dental pulp stem cells or pre-odontoblasts. However, in mice, PIEZO1 and PIEZO2 were ubiquitously detected and colocalized in odontoblasts. Intense immunoreactivity of PIEZO1 and PIEZO2 has been observed in human and murine periodontal ligaments. Our findings suggest that PIEZO1 and PIEZO2 may be mechanosensors/mechanotransducers in murine odontoblasts, as well as in the transmission of forces by the periodontal ligament in humans and mice.
Topics: Humans; Mice; Animals; Periodontal Ligament; Vimentin; Mechanotransduction, Cellular; Dental Pulp; Ion Channels
PubMed: 37975162
DOI: 10.1002/ar.25351 -
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 -
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 -
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 -
International Journal of Molecular... Feb 2024The extracellular matrix (ECM) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which... (Review)
Review
The extracellular matrix (ECM) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which cells sit, and composed of proteins (such as collagen), glycosaminoglycans, proteoglycans, minerals, and water. The ECM provides a fundamental framework for the cellular constituents of tissue and biochemical support to surrounding cells. The ECM is a highly dynamic structure that is constantly being remodeled. Matrix metalloproteinases (MMPs) are among the most important proteolytic enzymes of the ECM and are capable of degrading all ECM molecules. MMPs play a relevant role in physiological as well as pathological processes; MMPs participate in embryogenesis, morphogenesis, wound healing, and tissue remodeling, and therefore, their impaired activity may result in several problems. MMP activity is also associated with chronic inflammation, tissue breakdown, fibrosis, and cancer invasion and metastasis. The periodontium is a unique anatomical site, composed of a variety of connective tissues, created by the ECM. During periodontitis, a chronic inflammation affecting the periodontium, increased presence and activity of MMPs is observed, resulting in irreversible losses of periodontal tissues. MMP expression and activity may be controlled in various ways, one of which is the inhibition of their activity by an endogenous group of tissue inhibitors of metalloproteinases (TIMPs), as well as reversion-inducing cysteine-rich protein with Kazal motifs (RECK).
Topics: Humans; Matrix Metalloproteinases; Periodontitis; Periodontium; Extracellular Matrix; Collagen; Inflammation; Tissue Inhibitor of Metalloproteinases; GPI-Linked Proteins
PubMed: 38474009
DOI: 10.3390/ijms25052763 -
Journal of Dental Research Oct 2023The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within...
The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.
Topics: Animals; Epithelial Attachment; Gingiva; Mastication; Connective Tissue; Biology; Epithelium
PubMed: 37555395
DOI: 10.1177/00220345231185288