Role In Periodontitis Research Articles

Serum levels of antimicrobial peptides (Cathelicidins and Beta Defensins-1) in patients with periodontitis

Background: periodontitis is a multifactorial oral inflammatory disease characterized by the gradual loss of bone and eventual tooth loss. It starts with microbes and is then influenced by the environment. A diverse family of host defense major compounds known as antimicrobial peptides react quickly to combat microbial invasion and challenge. These little cationic peptides are crucial for the development of innate immunity. The goal of this study was to evaluate the blood levels of healthy individuals and patients with periodontitis for cathelicidins and human beta-defensin-1. In this case-control study, 35 healthy volunteers (matched exactly by age and sex to the patients) and 50 periodontitis patients (aged 20 to 59) participated. In this investigation, periodontal parameters such as plaque index, gingival index bleeding on probing, probing pocket depth, and clinical attachment loss were employed. The levels of cathelicidins and human beta-defensin-1 in patients and controls were estimated using ELISA after blood samples from all individuals were taken. The current findings showed that the mean levels of cathelicidin and human beta defensin-1 were significantly higher (P˂0.01) in the patient group compared to the control group, and that there was no significant correlation with all clinical periodontal parameters. These findings support the notion that antimicrobial peptides play a crucial role in periodontitis' inflammatory process.

IL-36 Regulates Neutrophil Chemotaxis and Bone Loss at the Oral Barrier

Tissue-specific mechanisms regulate neutrophil immunity at the oral barrier, which plays a key role in periodontitis. Although it has been proposed that fibroblasts emit a powerful neutrophil chemotactic signal, how this chemotactic signal is driven has not been clear. The objective of this study was to investigate the site-specific regulatory mechanisms by which fibroblasts drive powerful neutrophil chemotactic signals within the oral barrier, with particular emphasis on the role of the IL-36 family. The present study found that IL-36γ, agonist of IL-36R, could promote neutrophil chemotaxis via fibroblast. Single-cell RNA sequencing data disclosed that IL36G is primarily expressed in human and mouse gingival epithelial cells and mouse neutrophils. Notably, there was a substantial increase in IL-36γ levels during periodontitis. In vitro experiments demonstrated that IL-36γ specifically activates gingival fibroblasts, leading to chemotaxis of neutrophils. In vivo experiments revealed that IL-36Ra inhibited the infiltration of neutrophils and bone resorption, while IL-36γ promoted their progression in the ligature-induced periodontitis mouse model. In summary, these data elucidate the function of the site-enriched IL-36γ in regulating neutrophil immunity and bone resorption at the oral barrier. These findings provide new insights into the tissue-specific pathophysiology of periodontitis and offer a promising avenue for prevention and treatment through targeted intervention of the IL-36 family.

Circ_0036490 and DKK1 competitively bind miR-29a to promote lipopolysaccharides-induced human gingival fibroblasts injury

MicroRNA (miRNA) plays a regulatory role in periodontitis. This study aimed to explore whether miR-29a could affect lipopolysaccharides (LPSs)-induced injury in human gingival fibroblasts (HGFs) through the competitive endogenous RNAs (ceRNA) mechanism. Periodontal ligament (PDL) tissues and HGFs were derived from patients with periodontitis and healthy volunteers. Periodontitis cell model was established by treating HGFs with LPS. Expression levels of circ_0036490, miR-29a, and DKK1 were evaluated by the reverse transcription quantitative real-time PCR (RT-qPCR) method. Western blotting assay was performed to assess protein expression levels of pyroptosis-related proteins and Wnt signalling related proteins. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Concentration of lactate dehydrogenase (LDH), interleukin (IL)-1β, and IL-18 were determined by Enzyme-linked immunosorbent assay (ELISA). Pyroptosis rate were determined by flow cytometry assay to evaluate pyroptosis. The interaction between miR-29a and circ_0036490 or DKK1 was verified by dual-luciferase reporter and RNA pull-down assays. MiR-29a expression was lower in PDL tissues of patients with periodontitis than that in healthy group; likewise, miR-29a was also downregulated in LPS-treated HGFs. Overexpression of miR-29a increased cell viability and decreased pyroptosis of HGFs induced by LPS while inhibition of miR-29a exerted the opposite role. MiR-29a binds to circ_0036490 and elevation of circ_0036490 contributed to dysfuntion of LPS-treated HGFs and reversed the protection function of elevated miR-29a. In addition, miR-29a targets DKK1. Overexpression of DKK1 abrogated the effects of overexpressed miR-29a on cell vaibility, pyroptosis, and protein levels of Wnt signalling pathway of LPS-treated HGFs. Circ_0036490 and DKK1 competitively bind miR-29a to promote LPS-induced HGF injury in vitro. Wnt pathway inactivated by LPS was activated by miR-29a. Thence, miR-29a may be a promising target for periodontitis.

Hepatocyte growth factor is protective in early stage but bone-destructive in late stage of experimental periodontitis.

Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.

Mitochondria: An Emerging Unavoidable Link in the Pathogenesis of Periodontitis Caused by Porphyromonas gingivalis.

Porphyromonas gingivalis (P. gingivalis) is a key pathogen of periodontitis. Increasing evidence shows that P. gingivalis signals to mitochondria in periodontal cells, including gingival epithelial cells, gingival fibroblast cells, immune cells, etc. Mitochondrial dysfunction affects the cellular state and participates in periodontal inflammatory response through the aberrant release of mitochondrial contents. In the current review, it was summarized that P. gingivalis induced mitochondrial dysfunction by altering the mitochondrial metabolic state, unbalancing mitochondrial quality control, prompting mitochondrial reactive oxygen species (ROS) production, and regulating mitochondria-mediated apoptosis. This review outlines the impacts of P. gingivalis and its virulence factors on the mitochondrial function of periodontal cells and their role in periodontitis.

New Fangled Avatar of Neutrophils and its Role in Periodontitis

New Fangled Avatar of Neutrophils and its Role in Periodontitis

Potential Association of Maker Expression of Low-Density Neutrophils and Their Phenotypes in Patients with Periodontitis: Control Study.

Neutrophils play an important role in maintaining periodontal status in conditions of healthy homeostasis. They achieve their surveillance function by continuously migrating to the gingival sulcus and eradicating periodontal pathogens. In addition, neutrophils are considered an integral element in the pathogenesis of periodontal diseases. Among several neutrophil subsets, low-density neutrophils (LDN) have recently received attention and are linked with cancer, immunological, inflammatory, and infectious diseases. However, the presence, phenotypes, and potential role of LDN in the pathogenesis of periodontitis have not yet been investigated. To investigate the presence, subsets (normal, band, suppressive, and active), and phenotypes via marker expression surface protein known as the cluster of differentiation (CD) (CD16b, CD14, CD15, and CD62L) of LDN in patients with periodontitis. The observational case-control study was conducted to estimate the potential role of LDNs in periodontitis. Venous blood and periodontal indices were obtained from 40 healthy control individuals and 60 periodontitis patients. Subsequently, CD16b, CD62L, CD14, and CD15 expression on the surface of LDN was examined by multicolor flow cytometry, and their subsets were classified as "normal" (CD16brightCD62Lbright), "bands" (CD16dimCD62Lbright), "suppressive" (CD16brightCD62Ldim), and "active" (CD16brightCD62Lnegative). There was a significant difference in the expression of LDN markers for active and suppressive phenotypes, respectively, favoring periodontitis over the control group. In contrast, there were significantly higher levels of CD16b, CD62L, and CD15 ("normal") in the control group when compared with the periodontitis group. LDN was associated with periodontitis as it was significantly increased in the periodontitis group in comparison with the control group and was positively correlated with all periodontal parameters. Cells from both groups of patients (periodontitis and control) expressed a normal mature phenotype (CD16b + High, CD62L + High, CD15+, and CD14-). Regarding subsets, the normal LDN (CD16brightCD62Lbright) was the most predominant phenotype in both periodontitis and control groups. However, the active subset increased in periodontitis compared to normal, indicating their destructive role in periodontitis.

Upregulated ATF1 Promotes Lipopolysaccharide Induced Inflammatory Response and Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Regulating NF-κB Pathway.

Periodontitis is a chronic inflammatory disease resulting from bacterial plaque infection. While the involvement of activating transcription factor 1 (ATF1) has been extensively explored in various human diseases, its specific role in periodontitis remains unclear. This study aims to elucidate the expression and biological function of ATF1 in the context of periodontitis. Primary human periodontal ligament cells (hPDLCs) were procured from clinical samples and subsequently characterized. Following treatment with P. gingivalis lipopolysaccharide (LPS, 10 μg/mL), hPDLCs underwent transfection with either ATF1 vector or siRNA. The expression levels of ATF1 in LPS-treated hPDLCs or transfected cells were evaluated through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Inflammatory factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β), were quantified using Enzyme-linked Immunosorbent Assay (ELISA). The assessment of osteogenic proteins, such as runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteoprotegerin (OPG), as well as noncanonical nuclear factor-kappaB (NF-κB) pathway-related proteins (p65, p-p65, IkBα, p-IkBα), was conducted using western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry assays were employed to detect cell viability. LPS induced an inflammatory response and hindered the osteogenic differentiation of hPDLCs (p < 0.05, p < 0.01). Furthermore, ATF1 silencing enhanced cell proliferation and suppressed apoptosis in LPS-stimulated hPDLCs (p < 0.05, p < 0.01). ATF1 silencing not only restrained the inflammatory response but also promoted the osteogenic differentiation of LPS-stimulated hPDLCs (p < 0.05, p < 0.01). Importantly, ATF1 silencing effectively blocked the LPS-induced activation of the NF-κB signaling pathway (p < 0.05, p < 0.01, p < 0.001). ATF1 emerges as a promising treatment option, inhibiting the osteogenic differentiation of hPDLCs and mitigating the inflammatory response by preventing the phosphorylation of the NF-κB signaling pathway.

Evaluation of interleukin-6 in gingival crevicular fluid in patients with periodontitis

Introduction: Periodontal diseases are disease processes involving the periodontium, a term that describes the supportive apparatus surrounding a tooth. Periodontitis is when the periodontal condition has progressed beyond gingivitis into a chronic, destructive, and irreversible inflammatory disease state. The bacteria can then penetrate deeper into the tissues and surrounding periodontium, triggering a host response in an attempt to defend against the invading bacteria. Many inflammatory cytokines regulate periodontitis pathophysiology through a cross-talk between tissue and immune cells. Interleukin (IL)-6 is a vital cytokine regulating host response to bacterial infection. Aim: The current study aimed to quantify IL-6 levels in gingival crevicular fluid (GCF) and assess the correlation with periodontitis. Materials and Methods: There were 22 study subjects: 11 study subjects (with periodontitis) and 11 control subjects (with healthy periodontium). The commercial human IL-6 ELISA kit (Elabscience) was used to measure the level of IL-6 as ng IL-6/ml of GCF. Results and Discussion: The control group had a mean ± standard deviation level of IL-6 of 0.56 ± 0.29, whereas the study group had 1.58 ± 0.23. The difference was statistically significant (P &lt; 0.05). Conclusion: IL-6 assessment in GCF has an excellent prognostic role in periodontitis.

Human Umbilical Cord Mesenchymal Stem Cells and their Extracellular Vesicles Modulate Pro- and Anti-inflammatory Cytokines in Ligature-induced Periodontitis.

Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, ultimately leading to tooth loss. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) play a crucial role in periodontitis by modulating the activities of gum cells and the immune system. To investigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCSCs) and EVs in regulating the inflammatory response associated with periodontitis. hUCSCs were isolated, subjected to flow cytometry analysis of surface markers, and differentiated into adipocyte and osteocyte. hUCSC-EVs were isolated and characterized using flow cytometry and electron microscopy. A periodontitis animal model was established in 30 female C57Bl/6 mice. Experimental groups received hUCSCs or hUCSCs-EVs, or vehicles intravenously. Animals were monitored for 4 weeks, and the periodontal tissues were used to assess the effects of hUCSCs and hUCSCs-EVs on the expression of pro- (TNF-α, IFN-γ, and IL-17a) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-4). The secretion of these cytokines by splenocytes was also evaluated using ELISA. The levels of IL-17a, IFN-γ, and TNFα significantly reduced, while TGF-β and IL-10 significantly increased in the periodontal tissues of the hUCSC and hUCSCEVs-treated mice. The expression of TNF-α, IFN-γ, and IL-17a significantly decreased, while the production of IL-10 and TGF-β significantly increased in splenocytes from the hUCSC and EVs-treated mice. hUCSCs and their EVs have the potential to attenuate the inflammatory response associated with periodontitis, possibly by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory ones.

The Role of Periodontitis as Modifiable Risk Factor for Alzheimer’s Disease- A Recent Update

Alzheimer’s disease (AD) is among the most common form of dementia affecting geriatric population. Various studies have been carried out to understand the etiopathogenesis of the disease. However, no definite cause has been established and thereby, there is no definite treatment/cure available for eradication of same. The solution for managing the disease is to control the risk factors or triggering factors related to progression or worsening of the condition. Among various risk factors of AD, invasion of the oral pathogens in the brain tissue due to periodontitis (PD) has been associated as risk factor. Various studies had been carried out to state an association between PD and AD. Thereby, this article will discuss most recent evidences available to claim the role of PD as modifiable risk factor in mechanism of AD.

CCL5's Role in Periodontal Disease: A Narrative Review.

Persistent host inflammatory and immune responses to biofilm play a critical role in the mechanisms that govern soft and hard tissue destruction in periodontal disease. Among the less explored facets of these mechanisms are chemokines, including CCL5 (C-C motif chemokine ligand 5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. Despite its importance, there is currently no comprehensive review of the role of CCL5 in periodontitis in the literature. Therefore, this paper aims to fill this gap by summarizing the existing knowledge on the involvement of CCL5 in the onset and progression of periodontitis. In addition, we aim to stimulate interest in this relatively overlooked factor among periodontitis researchers, potentially accelerating the development of drugs targeting CCL5 or its receptors. The review examines the association of CCL5 with periodontitis risk factors, including aging, cigarette smoking, diabetes, and obesity. It discusses the involvement of CCL5 in pathological processes during periodontitis, such as connective tissue and bone destruction. The data show that CCL5 expression is observed in affected gums and gingival crevicular fluid of periodontitis patients, with bacterial activity contributing significantly to this increase, but the reviewed studies of the association between CCL5 expression and periodontal disease have yielded inconclusive results. Although CCL5 has been implicated in the pathomechanism of periodontitis, a comprehensive understanding of its molecular mechanisms and significance remains elusive, hindering the development of drugs targeting this chemokine or its receptors.

Granzyme B promotes matrix metalloproteinase-1 (MMP-1) release from gingival fibroblasts in a PAR1- and Erk1/2-dependent manner: A novel role in periodontal inflammation.

To gain insights into how proteases signal to connective tissues cells in the periodontium. The connective tissue degradation observed in periodontitis is largely due to matrix metalloproteinase (MMP) release by gingival fibroblasts. Granzyme B (GzmB) is a serine protease whose role in periodontitis is undefined. Human gingival crevicular fluid (GCF) samples were obtained from sites with periodontal disease and healthy control sites. GzmB was quantified in the GCF ([GzmB]GCF ) by ELISA. Gingival fibroblasts (GF) were cultured in the presence or absence of recombinant GzmB. Culture supernatants were analyzed by ELISA to quantify GzmB-induced release of interstitial collagenase (MMP-1). In some experiments, cells were pre-treated with the inhibitor PD98059 to block MEK/ERK signaling. The protease-activated receptor-1 (PAR-1) was blocked with ATAP-2 neutralizing antibody prior to GzmB stimulation. Systemic MMP-1 levels were measured in plasma from wild-type (WT) and granzyme-B-knockout (GzmB-/- ) mice. The [GzmB]GCF in human samples was ~4-5 fold higher at sites of periodontal disease (gingivitis/periodontitis) compared to healthy control sites, suggesting an association between GzmB and localized matrix degradation. GzmB induced a ~4-5-fold increase in MMP-1 secretion by cultured fibroblasts. GzmB induced phosphorylation of Erk1/2, which was abrogated by PD98059. GzmB-induced upregulation of MMP-1 secretion was also reduced by PD98059. Blockade of PAR-1 function by ATAP-2 abrogated the increase in MMP-1 secretion by GF. Circulating MMP-1 was similar in WT and GzmB-/- mice, suggesting that GzmB's effects on MMP-1 release are not reflected systemically. These data point to a novel GzmB-driven signaling pathway in fibroblasts in which MMP-1 secretion is upregulated in a PAR1- and Erk1/2-dependent manner.

Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway.

Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have anti‑inflammatory potential, but whether KA can inhibit macrophage pyroptosis and the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used to induce pyroptosis in THP‑1‑derived macrophages. KA or ML385 was used to pretreat macrophages, after which, cell viability, NOD‑like receptor protein 3 (NLRP3) inflammasome‑related protein expression, oxidative stress levels and nuclear factor erythroid 2‑related factor 2 (NRF2) expression were measured. The results showed that KA improved the LPS‑induced decrease in macrophage viability and lactate dehydrogenase release. KA prevented THP‑1 macrophage pyroptosis induced by LPS by reducing the expression of NLRP3, Gasdermin‑D, and Caspase1, and decreased the expression of inflammatory factors. KA suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction and increasing Heme Oxygenase 1 and glutathione levels. Moreover, KA promoted NRF2 translocation from the cytoplasm to the nucleus. In addition, the anti‑pyroptotic and antioxidant effects of KA were reversed by ML385 inhibition of NRF2. In the present study, it was found that KA significantly suppressed macrophage pyroptosis induced by LPS. It was further demonstrated that the anti‑pyroptotic effects of KA were mediated by activation of the NRF2 pathway.

Luteolin inhibits Porphyromonas gingivalis growth and alleviates alveolar bone destruction in experimental murine periodontitis.

Periodontal disease is a major oral infectious disease that destroys alveolar bones and causes tooth loss. Porphyromonas gingivalis is a key pathogen that plays a crucial role in periodontitis. In our previous study on the anti-P. gingivalis activity of flavonoid, luteolin, a major flavonoid in edible plants, inhibited the proteolytic activity of gingipains, the major virulence factor in P. gingivalis. This study demonstrated luteolin in vitro and in vivo anti-bacterial activities. Thus, luteolin inhibits planktonic growth and biofilm formation in P. gingivalis. Furthermore, oral administration of luteolin alleviated maxillary alveolar bone resorption (ABR) in murine periodontitis induced by P. gingivalis infection. These results indicate that luteolin may be a potential therapeutic compound that targets P. gingivalis by hindering its growth, biofilm formation, and ABR in the oral cavity.

Exosomal microRNA-223 from neutrophil-like cells inhibits osteogenic differentiation of PDLSCs through the cGMP-PKG signaling pathway.

Neutrophils-derived exosomes have been shown to cause tissue inflammation in many diseases, but their role in periodontitis, a neutrophil-mediated disease, is unknown. Here, we investigated the effect of neutrophil-like cells derived exosomes on osteogenic dysfunction of periodontal ligament stem cells (PDLSCs) in periodontitis. Neutrophil-like cells were derived from HL-60 cells by dimethylsulfoxide stimulation. Exosomes were isolated by ultracentrifugation and characterized using transmission electron microscopy, nanoflow cytometry and western blot. MicroRNA-223 (miR-223) expression were analyzed by real-time PCR. Western blot, alkaline phosphatase (ALP), and alizarin red staining were conducted to assess whether exosomes could affect the osteogenic differentiation of PDLSCs. The expression of miR-223 was inhibited in PDLSCs by transfecting with miR-223 inhibitor. Cyclic guanosine monophosphate (cGMP) expression was determined by enzyme-linked immunosorbent assay. We found that miR-223 was significantly increased in neutrophils and neutrophil-like cells derived exosomes. Treatment with exosomes derived from neutrophil-like cells upregulated miR-223 expression and inhibited the osteogenic differentiation of PDLSCs, while transfection with miR-223 inhibitor significantly promoted PDLSCs osteogenic differentiation. In addition, co-treatment with KT5823, a cGMP-PKG pathway inhibitor, markedly abrogated the rescue effects of miR-223 inhibitor on the osteogenic differentiation of PDLSCs. Our findings suggest that neutrophil-like cells derived exosomes might inhibit osteogenic differentiation of PDLSCs by transporting miR-223 and regulating the cGMP-PKG signaling pathway.

The Gum-Gut Axis: Periodontitis and the Risk of Gastrointestinal Cancers.

Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral microbiome and immune-inflammatory pathways related to periodontitis may impact the pathophysiology of the gastrointestinal tract and its accessory organs through the so-called "gum-gut axis". In addition to the hematogenous spread of periodontal pathogens and inflammatory cytokines, recent research suggests that oral pathobionts may translocate to the gastrointestinal tract through saliva, possibly impacting neoplastic processes in the gastrointestinal, liver, and pancreatic systems. The exact mechanisms by which oral pathogens contribute to the development of digestive tract cancers are not fully understood but may involve dysbiosis of the gut microbiome, chronic inflammation, and immune modulation/evasion, mainly through the interaction with T-helper and monocytic cells. Specifically, keystone periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, are known to interact with the molecular hallmarks of gastrointestinal cancers, inducing genomic mutations, and promote a permissive immune microenvironment by impairing anti-tumor checkpoints. The evidence gathered here suggests a possible role of periodontitis and oral dysbiosis in the carcinogenesis of the enteral tract. The "gum-gut axis" may therefore represent a promising target for the development of strategies for the prevention and treatment of gastrointestinal cancers.

CCL2 is a key regulator and therapeutic target for periodontitis.

Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokineligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingivareversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1β. CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.

Efektivitas berkumur Ekstrak Kurma Ajwa (Phoenix Dactylifera L.) terhadap penurunan indeks plak pada mahasiswa pengguna Ortodonti Cekat di FKG UMI Angkatan 2019-2021

Dental and oral health is an integral part of health in general. It is very important to maintain dental health because it is closely related to diseases in the oral cavity. According to a survey conducted by the Indonesian National Dental Research Institute (NIDR) in Indonesia, as many as 70% of people suffer from periodontal disease, this causes periodontal disease to be the second main problem that occurs in society. Some causes of periodontal disease include systemic disease, medications, malnutrition, and dental plaque. The main factor that plays a role in periodontal disease is dental plaque. One way to maintain healthy teeth and mouth is to rinse your mouth. According to the World Health Organization (WHO), 80% of the world's population is more dependent on the use of traditional medicine, because natural or traditional medicine has no side effects. Alternatives that meet these criteria are herbal ingredients, one of which is Ajwa Dates. The aim of this study was to determine the reduction in plaque index in orthodontic students at FKG UMI after gargling with Ajwa date extract. Materials and Methods: This research is quasi-experimental with pre-test and post-test group design and sampling using purposive sampling. The statistical test used is the Independent T–Test. The results obtained from the Independent T-Test showed that between before and after gargling Ajwa date extract there was a significant decrease in plaque index (p=0.000). Based on the Independent T-Test, Ajwa date extract is effective in reducing the plaque index. So it can be concluded that Ajwa date extract can reduce the plaque index in orthodontic users.

Osteoprotective Role of the Mir338 Cluster Ablation during Periodontitis

Periodontitis is a chronic inflammatory disease that compromises the integrity of the supporting tissues of the teeth and leads to the loss of the alveolar bone. The Mir338 cluster has been proven to be a potential target for the treatment of osteoporosis and is also enriched in gingival tissues with periodontitis; however, its role in periodontitis remains unknown. Here, we aimed to use periodontitis as a model to expand our understanding of the Mir338 cluster in osteoimmunology and propose a new target to protect against bone loss during periodontitis progression. Significant enrichment of the Mir338 cluster was validated in gingival tissues from patients with chronic periodontitis and a ligature-induced periodontitis mouse model. In vivo, attenuation of alveolar bone loss after 7 d of ligature was observed in the Mir338 cluster knockout (KO) mice. Interestingly, immunofluorescence and RNA sequencing showed that ablation of the Mir338 cluster reduced osteoclast formation and elevated the inflammatory response, with enrichment of IFN-γ and JAK-STAT signaling pathways. Ablation of the Mir338 cluster also skewed macrophages toward the M1 phenotype and inhibited osteoclastogenesis via Stat1 in vitro and in vivo. Furthermore, the local administration of miR-338-3p antagomir prevented alveolar bone loss from periodontitis. In conclusion, the Mir338 cluster balanced M1 macrophage polarization and osteoclastogenesis and could serve as a novel therapeutic target against periodontitis-related alveolar bone loss.