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Periodontal disease (PD) is caused by microbial dysbiosis and accompanying adverse inflammatory responses. Due to its high incidence and association with various systemic diseases, disease-modifying treatments that modulate dysbiosis serve as promising therapeutic approaches. In this study, to simulate the pathophysiological situation, we established a "temporary ligature plus oral infection model" that incorporates a temporary silk ligature and oral infection with a cocktail of live Tannerella forsythia (Tf), Pophyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn) in mice and tested the efficacy of a new trivalent mucosal vaccine. It has been reported that Tf, a red complex pathogen, amplifies periodontitis severity by interacting with periodontopathic bacteria such as Pg and Fn. Here, we developed a recombinant mucosal vaccine targeting a surface-associated protein, BspA, of Tf by genetically combining truncated BspA with built-in adjuvant flagellin (FlaB). To simultaneously induce Tf-, Pg-, and Fn-specific immune responses, it was formulated as a trivalent mucosal vaccine containing Tf-FlaB-tBspA (BtB), Pg-Hgp44-FlaB (HB), and Fn-FlaB-tFomA (BtA). Intranasal immunization with the trivalent mucosal vaccine (BtB + HB + BtA) prevented alveolar bone loss and gingival proinflammatory cytokine production. Vaccinated mice exhibited significant induction of Tf-tBspA-, Pg-Hgp44-, and Fn-tFomA-specific IgG and IgA responses in the serum and saliva, respectively. The anti-sera and anti-saliva efficiently inhibited epithelial cell invasion by Tf and Pg and interfered with biofilm formation by Fn. The flagellin-adjuvanted trivalent mucosal vaccine offers a novel method for modulating dysbiotic bacteria associated with periodontitis. This approach leverages the adjuvant properties of flagellin to enhance the immune response, aiming to restore a balanced microbial environment and improve periodontal health. [ABSTRACT FROM AUTHOR]

Aim: Among numerous constituents of Panax ginseng, a constituent named Ginsenoside Rb1 (G‐Rb1) has been studied to diminish inflammation associated with diseases. This study investigated the anti‐inflammatory properties of G‐Rb1 on human dental pulp cells (hDPCs) exposed to lipopolysaccharide (LPS) and aimed to determine the underlying molecular mechanisms. Methodology: The KEGG pathway analysis was performed after RNA sequencing in G‐Rb1‐ and LPS‐treated hDPCs. Reverse‐transcription polymerase chain reaction (RT–PCR) and western blot analysis were used for the assessment of cell adhesion molecules and inflammatory cytokines. Statistical analysis was performed with one‐way ANOVA and the Student–Newman–Keuls test. Results: G‐Rb1 did not exhibit any cytotoxicity within the range of concentrations tested. However, it affected the levels of TNF‐α, IL‐6 and IL‐8, as these showed reduced levels with exposure to LPS. Additionally, less mRNA and protein expressions of vascular cell adhesion molecule‐1 (VCAM‐1) and intercellular adhesion molecule‐1 (ICAM‐1) were shown. With the presence of G‐Rb1, decreased levels of PI3K/Akt, phosphorylated IκBα and p65 were also observed. Furthermore, phosphorylated ERK and JNK by LPS were diminished within 15, 30 and 60 min of G‐Rb1 exposure; however, the expression of non‐phosphorylated ERK and JNK remained unchanged. Conclusions: G‐Rb1 suppressed the LPS‐induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF–κB transcription factors, ERK and JNK of MAPK signalling in hDPCs. [ABSTRACT FROM AUTHOR]

Several members of the transforming growth factor beta (TGF‐β) superfamily regulate the proliferation, differentiation, and function of bone‐forming osteoblasts and bone‐resorbing osteoclasts. However, it is still unknown whether Nodal, a member of the TGF‐β superfamily, serves a function in bone cells. In this study, we found that Nodal did not have any function in osteoblasts but instead negatively regulated osteoclast differentiation. Nodal inhibited RANKL‐induced osteoclast differentiation by downregulating the expression of pro‐osteoclastogenic genes, including c‐fos, Nfatc1, and Blimp1, and upregulating the expression of antiosteoclastogenic genes, including Bcl6 and Irf8. Nodal activated STAT1 in osteoclast precursor cells, and STAT1 downregulation significantly reduced the inhibitory effect of Nodal on osteoclast differentiation. These findings indicate that Nodal activates STAT1 to downregulate or upregulate the expression of pro‐osteoclastogenic or antiosteoclastogenic genes, respectively, leading to the inhibition of osteoclast differentiation. Moreover, the inhibitory effect of Nodal on osteoclast differentiation contributed to the reduction of RANKL‐induced bone loss in vivo. [ABSTRACT FROM AUTHOR]

Background: To evaluate the current evidence on clear aligners and root resorption using 3D and/or combined 2D and 3D methods from available systematic reviews and meta-analyses and to determine the relationship between root resorption and clear aligners using the AMSTAR 2 tool. Methods: A comprehensive literature search of systematic reviews investigating aligners and root resorption, published up until 31 December 2022, was conducted. The following electronic databases were searched: MEDLINE via PubMed, EMBASE, Google Scholar, Science Direct, Web of Science, Scopus, LIVIVO, and LILACS. There were no language restrictions. The inclusion criteria were restricted to studies focusing on root resorption utilizing either 3D methods exclusively or a combination of 2D and 3D techniques. Data were screened and analyzed for quality using the "A Measurement Tool to Assess Systematic Reviews (AMSTAR 2)" tool. Data extraction was conducted independently by two authors. The gathered information was categorized and synthesized narratively based on the primary findings elucidated within the reviews. Results: Out of a total of 1221 potentially eligible studies initially identified, 4 systematic reviews met the inclusion criteria following the exclusion of irrelevant studies. Among these, two systematic reviews (50%) were classified as low-quality, while the remaining two (50%) were deemed to be of critically low quality. Conclusions: Based on the findings of four systematic reviews, the root resorption rate was lower with the use of clear aligners than with fixed aligners. It is advisable to approach the interpretation of this conclusion with caution, as the quality of the available evidence is assessed to be very low. Higher quality systematic reviews are needed to substantiate this conclusion. [ABSTRACT FROM AUTHOR]

Osteoarthritis--the most common form of age-related degenerative whole-joint disease.sup.1--is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and subchondral bone remodelling.sup.2,3. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are largely unknown. Although osteoarthritis is currently considered to be associated with metabolic disorders, direct evidence for this is lacking, and the role of cholesterol metabolism in the pathogenesis of osteoarthritis has not been fully investigated.sup.4-6. Various types of cholesterol hydroxylases contribute to cholesterol metabolism in extrahepatic tissues by converting cellular cholesterol to circulating oxysterols, which regulate diverse biological processes.sup.7,8. Here we show that the CH25H-CYP7B1-ROR[alpha] axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator of the pathogenesis of osteoarthritis. Osteoarthritic chondrocytes had increased levels of cholesterol because of enhanced uptake, upregulation of cholesterol hydroxylases (CH25H and CYP7B1) and increased production of oxysterol metabolites. Adenoviral overexpression of CH25H or CYP7B1 in mouse joint tissues caused experimental osteoarthritis, whereas knockout or knockdown of these hydroxylases abrogated the pathogenesis of osteoarthritis. Moreover, retinoic acid-related orphan receptor alpha (ROR[alpha]) was found to mediate the induction of osteoarthritis by alterations in cholesterol metabolism. These results indicate that osteoarthritis is a disease associated with metabolic disorders and suggest that targeting the CH25H-CYP7B1-ROR[alpha] axis of cholesterol metabolism may provide a therapeutic avenue for treating osteoarthritis.In experimentally induced osteoarthritis, chondrocytes show increased uptake and metabolism of cholesterol, implicating the CH25H-CYP7B1-ROR[alpha] axis in the pathogenesis of osteoarthritis., Author(s): Wan-Su Choi [sup.1] , Gyuseok Lee [sup.1] [sup.2] , Won-Hyun Song [sup.2] , Jeong-Tae Koh [sup.2] , Jiye Yang [sup.1] , Ji-Sun Kwak [sup.1] , Hyo-Eun Kim [sup.1] , [...]

Human monocyte chemoattractant protein‐1 (MCP‐1) in mice has two orthologs, MCP‐1 and MCP‐5. MCP‐1, which is highly expressed in osteoclasts rather than in osteoclast precursor cells, is an important factor in osteoclast differentiation. However, the roles of MCP‐5 in osteoclasts are completely unknown. In this study, contrary to MCP‐1, MCP‐5 was downregulated during receptor activator of nuclear factor kappa B ligand (RANKL)‐induced osteoclast differentiation and was considered an inhibitory factor in osteoclast differentiation. The inhibitory role of MCP‐5 in osteoclast differentiation was closely related to the increase in Ccr5 expression and the inhibition of IκB degradation by RANKL. Transgenic mice expressing MCP‐5 controlled by Mx‐1 promoter exhibited an increased bone mass because of a decrease in osteoclasts. This result strongly supported that MCP‐5 negatively regulated osteoclast differentiation. MCP‐5 also prevented severe bone loss caused by RANKL. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between obesity and self‐rated oral health (SROH). This study examined the cross‐sectional associations between body mass index (BMI) and SROH in Korean adults. Materials and methods: This study used data from 217 304 adults (100 110 men and 117 194 women aged > 19 years) from the 2017 Korean Community Health Survey. Participants were categorised into six ordinal groups based on BMI: underweight (<18.5 kg/m2), normal weight (18.5‐22.9 kg/m2), overweight (23.0‐24.9 kg/m2), obese‐I (25.0‐27.4 kg/m2), obese‐II (27.5‐29.9 kg/m2) or obese‐III (≥30.0 kg/m2). SROH was assessed using responses to the question, "How do you rate your oral health, including your teeth and gums?" rated on a 5‐point scale. SROH was categorised as "good" (reported as "fair," "good" or "very good") or "poor" or "very poor." Age‐ and sex‐stratified associations between BMI categories and poor SROH were assessed using ordinal logistic regression analysis with sampling weights. Results: The age‐adjusted odds ratio (OR) for poor SROH according to BMI levels was lowest in the overweight group in both men and women. In men, the OR for poor SROH was 2.03 (99% confidence interval [CI], 1.72‐2.39) in the underweight group, 1.17 (99% CI, 1.17‐1.25) in the normal group, 1.05 (99% CI, 0.98‐1.13) in the obese‐I group, 1.08 (99% CI, 0.98‐1.18) in the obese‐II group and 1.36 (99% CI, 1.20‐1.55) in the obese‐III group. In women, the OR was 1.18 (99% CI, 1.07‐1.31) in the underweight group, 1.01 (99% CI, 0.95‐1.07) in the normal group, 1.07(99% CI, 0.99‐1.16) in the obese‐I group, 1.16 (99% CI, 1.04‐1.30) in the obese‐II group and 1.39 (99% CI, 1.20‐1.62) in the obese‐III group. From the restricted cubic spline models in both sexes, BMI showed a J‐shaped association with poor and very poor SROH in men and women. In a stratified analysis by age group and sex, men and older women in the underweight group had poorer SROH than those in overweight group. Conclusion: In a nationally representative sample of Korean adults, there was a J‐shaped association between BMI and poor SROH, with the highest risk in the underweight group amongst men and in the obese‐III group amongst women. Furthermore, in men and women over 65 years of age, underweight and obesity were associated with poorer SROH. [ABSTRACT FROM AUTHOR]

There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1β, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis. [ABSTRACT FROM AUTHOR]

The engulfment adaptor phosphotyrosine‐binding domain containing 1 (GULP1) is an adaptor protein involved in the engulfment of apoptotic cells via phagocytosis. Gulp1 was first found to promote the phagocytosis of apoptotic cells by macrophages, and its role in various tissues, including neurons and ovaries, has been well studied. However, the expression and function of GULP1 in bone tissue are poorly understood. Consequently, to determine whether GULP1 plays a role in the regulation of bone remodeling in vitro and in vivo, we generated Gulp1 knockout (KO) mice. Gulp1 was expressed in bone tissue, mainly in osteoblasts, while its expression is very low in osteoclasts. Microcomputed tomography and histomorphometry analysis in 8‐week‐old male Gulp1 KO mice revealed a high bone mass in comparison with male wild‐type (WT) mice. This was a result of decreased osteoclast differentiation and function in vivo and in vitro as confirmed by a reduced actin ring and microtubule formation in osteoclasts. Gas chromatography‐mass spectrometry analysis further showed that both 17β‐estradiol (E2) and 2‐hydroxyestradiol levels, and the E2/testosterone metabolic ratio, reflecting aromatase activity, were also higher in the bone marrow of male Gulp1 KO mice than in male WT mice. Consistent with mass spectrometry analysis, aromatase enzymatic activity was significantly higher in the bone marrow of male Gulp1 KO mice. Altogether, our results suggest that GULP1 deficiency decreases the differentiation and function of osteoclasts themselves and increases sex steroid hormone‐mediated inhibition of osteoclast differentiation and function, rather than affecting osteoblasts, resulting in a high bone mass in male mice. To the best of our knowledge, this is the first study to explore the direct and indirect roles of GULP1 in bone remodeling, providing new insights into its regulation. [ABSTRACT FROM AUTHOR]

Xanthones are secondary metabolites isolated from the peel of mangosteen showing medicinal potencies. Alpha-mangostin (α-MG) is the most plentiful xanthone, which has been reported to possess anti-inflammatory, anti-oxidant, and anti-bacterial activities. We aimed to investigate the anti-inflammatory effects of xanthones on LPS-treated hDPCs. Cell viability was determined using the WST-1 assay. The mRNA and protein expression profiles of inflammatory mediators were evaluated using quantitative real-time polymerase chain reaction (qPCR) and Western blot analysis. Anti-inflammatory effects were assessed using the Western blot analysis to examine underlying mechanisms. A one-way analysis of variance followed by Tukey's post hoc test was used to determine statistically significant differences (p < 0.05). The study found no significant differences between the cytotoxic effects in the α-MG-treated groups and controls. The mRNA and protein expression levels of inflammatory markers in the α-MG treated groups decreased. α-MG significantly inhibited LPS-induced phosphorylation of proteins associated with the MAPK and NF-κB pathways. This study suggests that α-MG exerts anti-inflammatory effects by suppressing the MAPK and NF-κB signaling pathways in LPS-treated hDPCs. [ABSTRACT FROM AUTHOR]