Search

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]

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 Methods Results Conclusion Osteoarthritis (OA) is the most common degenerative disease worldwide, with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol‐lowering drugs in suppressing OA development in mice, and uncover the cholesterol‐lowering mechanisms that effectively impede OA progression.Five clinically approved cholesterol‐lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to mice with OA who underwent destabilization of the medial meniscus induction and were fed a 2% high‐cholesterol diet. Gene expression linked to cholesterol metabolism was determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra‐articular injection of either its inhibitor or adenovirus.Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol‐lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high‐density lipoprotein cholesterol that are crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via down‐regulation of apolipoprotein A1–binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression.Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for patients with OA. [ABSTRACT FROM AUTHOR]

Cell-based tissue engineering often requires the use of scaffolds to provide a three-dimensional (3D) framework for cell proliferation and tissue formation. Polycaprolactone (PCL), a type of polymer, has good printability, favorable surface modifiability, adaptability, and biodegradability. However, its large-scale applicability is hindered by its hydrophobic nature, which affects biological properties. Composite materials can be created by adding bioactive materials to the polymer to improve the properties of PCL scaffolds. Osteolectin is an odontogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR+ cells into osteoblasts. Therefore, the aim of this study was to evaluate whether 3D-printed PCL/osteolectin scaffolds supply a suitable microenvironment for the odontogenic differentiation of human dental pulp cells (hDPCs). The hDPCs were cultured on 3D-printed PCL scaffolds with or without pores. Cell attachment and cell proliferation were evaluated using EZ-Cytox. The odontogenic differentiation of hDPCs was evaluated by alizarin red S staining and alkaline phosphatase assays. Western blot was used to evaluate the expression of the proteins DSPP and DMP-Results: The attachment of hDPCs to PCL scaffolds with pores was significantly higher than to PCL scaffolds without pores. The odontogenic differentiation of hDPCs was induced more in PCL/osteolectin scaffolds than in PCL scaffolds, but there was no statistically significant difference. 3D-printed PCL scaffolds with pores are suitable for the growth of hDPCs, and the PCL/osteolectin scaffolds can provide a more favorable microenvironment for the odontogenic differentiation of hDPCs., (© 2024 IOP Publishing Ltd.)

This study investigated the effectiveness of bone regeneration upon the application of leptin and osteolectin to a three-dimensional (3D) printed poly( ϵ -caprolactone) (PCL) scaffold. A fused deposition modeling 3D bioprinter was used to fabricate scaffolds with a diameter of 4.5 mm, a height of 0.5 mm, and a pore size of 420-520 nm using PCL (molecular weight: 43 000). After amination of the scaffold surface for leptin and osteolectin adhesion, the experimental groups were divided into the PCL scaffold (control), the aminated PCL (PCL/Amine) scaffold, the leptin-coated PCL (PCL/Leptin) scaffold, and the osteolectin-coated PCL (PCL/Osteo) scaffold. Next, the water-soluble tetrazolium salt-1 (WST-1) assay was used to assess cell viability. All groups exhibited cell viability rates of >100%. Female 7-week-old Sprague-Dawley rats were used for in vivo experiments. Calvarial defects were introduced on the rats' skulls using a 5.5 mm trephine bur. The rats were divided into the PCL (control), PCL/Leptin, and PCL/Osteo scaffold groups. The scaffolds were then inserted into the calvarial defect areas, and the rats were sacrificed after 8-weeks to analyze the defect area. Micro-CT analysis indicated that the leptin- and osteolectin-coated scaffolds exhibited significantly higher bone regeneration. Histological analysis revealed new bone and blood vessels in the calvarial defect area. These findings indicate that the 3D-printed PCL scaffold allows for patient-customized fabrication as well as the easy application of proteins like leptin and osteolectin. Moreover, leptin and osteolectin did not show cytotoxicity and exhibited higher bone regeneration potential than the existing scaffold., (© 2024 IOP Publishing Ltd.)