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International Journal of Molecular... Jul 2023Gingival-derived mesenchymal stem cells (GMSCs) have strong self-renewal, multilineage differentiation, and immunomodulatory properties and are expected to be applied in...
Gingival-derived mesenchymal stem cells (GMSCs) have strong self-renewal, multilineage differentiation, and immunomodulatory properties and are expected to be applied in anti-inflammatory and tissue regeneration. However, achieving the goal of using endogenous stem cells to treat diseases and even regenerate tissues remains a challenge. Resveratrol is a natural compound with multiple biological activities that can regulate stem cell immunomodulation when acting on them. This study found that resveratrol can reduce inflammation in human gingival tissue and upregulate the stemness of GMSCs in human gingiva. In cell experiments, it was found that resveratrol can reduce the expression of TLR4, TNFα, and NFκB and activate ERK/Wnt crosstalk, thereby alleviating inflammation, promoting the proliferation and osteogenic differentiation ability of GMSCs, and enhancing their immunomodulation. These results provide a new theoretical basis for the application of resveratrol to activate endogenous stem cells in the treatment of diseases in the future.
Topics: Humans; Cell Differentiation; Cells, Cultured; Gingiva; MAP Kinase Signaling System; Osteogenesis; Periodontitis; Resveratrol
PubMed: 37511053
DOI: 10.3390/ijms241411294 -
International Journal of Oral Science Oct 2023X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization...
X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Topics: Mice; Male; Female; Animals; Familial Hypophosphatemic Rickets; Bone and Bones; Tooth; Periodontal Ligament
PubMed: 37813865
DOI: 10.1038/s41368-023-00252-1 -
Journal of Cellular Physiology Sep 2023Repair of orthodontic external root resorption and periodontal tissue dysfunction induced by mechanical force remains a clinical challenge. Cementoblasts are vital in...
Repair of orthodontic external root resorption and periodontal tissue dysfunction induced by mechanical force remains a clinical challenge. Cementoblasts are vital in cementum mineralization, a process important for restoring damaged cementum. Despite autophagy plays a role in mineralization under various environmental stimuli, the underlying mechanism of autophagy in mediating cementoblast mineralization remains unclear. Here we verified that murine cementoblasts exhibit compromised mineralization under compressive force. Autophagy was indispensable for cementoblast mineralization, and autophagic activation markedly reversed cementoblast mineralization and prevented cementum damage in mice during tooth movement. Subsequently, messenger RNA sequencing analyses identified periostin (Postn) as a mediator of autophagy and mineralization in cementoblasts. Cementoblast mineralization was significantly inhibited following the knockdown of Postn. Furthermore, Postn silencing suppressed Wnt signaling by modulating the stability of β-catenin. Together our results highlight the role of autophagy in cementoblast mineralization via Postn/β-catenin signaling under compressive force and may provide a new strategy for the remineralization of cementum and regeneration of periodontal tissue.
Topics: Animals; Mice; beta Catenin; Cell Differentiation; Cell Line; Dental Cementum; Wnt Signaling Pathway; Calcification, Physiologic; Cell Adhesion Molecules; Autophagy; Compressive Strength
PubMed: 37475648
DOI: 10.1002/jcp.31075 -
Journal of Periodontal Research Apr 2024The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of...
OBJECTIVE
The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis.
BACKGROUND DATA
Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen-reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature-induced periodontitis. Therefore, anti-inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease.
METHODS
We used an animal model of ligature-induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 μg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement-enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF-α levels in plasma were determined using specific rat enzyme-linked immunosorbent assays (ELISA). OXT receptors, IL-6, IL-1β, and TNF-α expression were determined in gingival tissues by semiquantitative or real-time PCR.
RESULTS
We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis-induced increased gum expression of oxytocin receptors, TNF-α, IL-6, and IL-1β (p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model.
CONCLUSIONS
Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature-induced periodontitis.
Topics: Rats; Male; Animals; Oxytocin; Tumor Necrosis Factor-alpha; Receptors, Oxytocin; Disease Models, Animal; Periodontitis; Gingiva; Alveolar Bone Loss; Alveolar Process; Inflammation Mediators
PubMed: 38226427
DOI: 10.1111/jre.13212 -
Journal of Bone and Mineral Research :... Aug 2023Kangfuxin (KFX) shows potential in wound healing, but its role in socket healing is unclear. This research finds increased bone mass, mineralization, and collagen...
Kangfuxin (KFX) shows potential in wound healing, but its role in socket healing is unclear. This research finds increased bone mass, mineralization, and collagen deposition in KFX-treated mice. Mouse bone marrow mesenchymal stem cells, human periodontal ligament stem cells (hPDLSCs), and human dental pulp stem cells (hDPSCs) are treated with KFX under osteogenic induction. RNA-sequencing reveals upregulated chemokine-related genes, with a threefold increase in chemokine (C-C motif) ligand 2 (Ccl2). The conditioned medium (CM) of hPDLSCs and hDPSCs treated with KFX promotes endothelial cell migration and angiogenesis. Ccl2 knockdown abolishes CM-induced endothelial cell migration and angiogenesis, which can be reversed by recombinant CCL2 treatment. KFX-treated mice showed increased vasculature. In conclusion, KFX increases the expression of CCL2 in stem cells, promoting bone formation and mineralization in the extraction socket by inducing endothelial cell angiogenesis. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Animals; Mice; Periodontal Ligament; Up-Regulation; Chemokine CCL2; Stem Cells; Wound Healing; Osteogenesis; Cell Differentiation
PubMed: 37221128
DOI: 10.1002/jbmr.4860 -
TouchREVIEWS in Endocrinology Apr 2024Periodontitis is a chronic inflammatory disease of the periodontium, or the supportive tissues around the tooth. This disease has been related to different risk factors,... (Review)
Review
Periodontitis is a chronic inflammatory disease of the periodontium, or the supportive tissues around the tooth. This disease has been related to different risk factors, such as the presence of plaque and calculus, tobacco smoking, low socioeconomic status, and the immune state of the host. Importantly, the chronic inflammatory environment generated by periodontitis may lead to tooth loss and diverse systemic complications, such as cardiovascular disease, osteoarthritis and metabolic disease. Recent investigations have supported the role of obesity as a risk factor for periodontitis. Furthermore, studies have found obesity to compromise healing after periodontal therapy; however, the mechanisms underlying this association are not well understood. Proteins called 'adipokines' could be the factor linking obesity to periodontitis. Adipokines are bioactive molecules with hormonal properties and a structure similar to cytokines produced by the adipose tissue. Although adipokines have both pro-and anti-inflammatory effects, the shift towards pro-inflammatory actions occurs when the adipose tissue becomes pathological, as observe in the progression of conditions such as obesity or adiposopathy. This article reviews the role of adipokines in the pathophysiology and progression of periodontitis by focusing on their impact on inflammation and the molecular mechanisms through which adipokines contribute to the onset and development of periodontitis.
PubMed: 38812668
DOI: 10.17925/EE.2024.20.1.7 -
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 Surgery... Jun 2024Periodontitis, a chronic inflammatory disease of the gums affects both the ligament and alveolar bone. A severe form of periodontal disease affects a strikingly high... (Review)
Review
Periodontitis, a chronic inflammatory disease of the gums affects both the ligament and alveolar bone. A severe form of periodontal disease affects a strikingly high number of one billion adults globally. The disease permutes both the soft and hard tissues of the oral cavity leading to localized and systemic diseases. Periodontitis has a deleterious impact on systemic health causing diabetes, cardiovascular diseases (CVD), and other disease. The cause of the enhanced inflammatory process is due to dysbiosis and an unregulated immune response. Innate immune response and T cells trigger uninhibited cytokine release causing an unwarranted inflammatory response. The RANK- RANKL interaction between osteoblasts, immune cells, and progenitor osteoclasts results in the maturation of osteoclasts, which promote bone resorption. It is well established that dysbiosis of the oral cavity has been implicated in periodontitis. But emerging reports suggest that the pulmonary pathogen, Mycobacterium tuberculosis (Mtb), causes extrapulmonary diseases such as periodontitis. Many clinical case reports advocate the involvement of Mtb in periodontitis, which poses a threat with the surge of tuberculosis in HIV and other immunocompromised individuals. Fostering a better understanding of the mechanism, causative agents and control on inflammatory response is imperative in the prevention and treatment of periodontitis.
Topics: Humans; Periodontitis; Mycobacterium tuberculosis; Tuberculosis
PubMed: 38231241
DOI: 10.1097/JS9.0000000000001122 -
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