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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]

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]