Periodontitis is a common infectious disease. Recent studies have indicated that the progression of periodontitis may be regulated by interactions between host immunity and periodontopathic bacteria. Although periodontopathic bacteria can destroy periodontal tissue, a dysfunctional host immune response triggered by the bacteria can lead to more severe and persistent destruction. Toll-like receptors (TLRs), a type of pattern recognition receptor (PRR) that recognizes pathogens, have been implicated in host innate immune responses to periodontopathic bacteria and in the activation of adaptive immunity. TLR-targeted drugs may hold promise to treat periodontal disease. This review summarizes recent studies on the role of TLRs in periodontitis and discusses areas needing further research. We believe TLRs may be an effective biomarker for the prevention, diagnosis, and treatment of periodontitis in the near future.

Silicon-based materials and their oxides are widely used in drug delivery, dietary supplements, implants and dental fillers. Silica nanoparticles (SiNPs) interact with immunocompetent cells and induce immunotoxicity. However, the toxic effects of SiNPs on the immune system have been inadequately reviewed. The toxicity of SiNPs to the immune system depends on their physicochemical properties and the cell type. Assessments of immunotoxicity include determining cell dysfunctions, cytotoxicity and genotoxicity. This review focuses on the immunotoxicity of SiNPs and investigates the underlying mechanisms. The main mechanisms were proinflammatory responses, oxidative stress and autophagy. Considering the toxicity of SiNPs, surface and shape modifications may mitigate the toxic effects of SiNPs, providing a new way to produce these nanomaterials with less toxic impaction.

Zinc oxide nanoparticles (ZnO NPs) are nanomaterials that are widely used in many fields. ZnO NPs are ion-shedding particles, and zinc ions produce important and potent effects that differ from those of other metal or metal oxide NPs. Several studies have reported the toxicological effects of ZnO NPs administered via several different routes, including orally, dermally, by pulmonary absorption, intraperitoneally, and intravenously. Some potential routes for human exposure have produced various toxic effects in animal models. Moreover, several in vitro studies using a range of cell lines have reported the mechanisms underlying ZnO NP toxicity. Zinc ions play a very important role in ZnO NP toxicity, although the effects of the particulate form cannot be excluded. A crucial determinant of toxicity is the solubility of ZnO NPs, which is influenced by various factors, including the pH of the environment in tissues, cells, and organelles. In addition to the inflammatory responses and oxidative stress known to be induced by ZnO NPs, these NPs also exhibit some positive anti-inflammatory, anti-diabetic, and pro-coagulant effects at sub-toxic doses; these effects are probably induced by zinc ions, which are an essential element in cell homeostasis. It is highly likely that there are additional distinct mechanisms at sub-toxic doses and concentrations, which may be concealed or altered by the toxic effects observed at higher levels of ZnO NPs. Furthermore, many signaling pathway molecules associated with necrosis and apoptosis can be activated, leading to cell death. This review presents the status of ZnO NP toxicology and highlights areas requiring further investigation.

Due to the widespread applications of zinc oxide nanoparticles (ZnO NPs), the potential exposure of workers, consumers, and scientists to these particles has increased. This potential for exposure has attracted extensive attention in the science community. Many studies have examined the toxicological profile of ZnO NPs in the immune system, digestive system, however, information regarding the toxicity of ZnO NPs in the nervous system is scarce. In this study, we detected the cytotoxicity of two types of ZnO NPs of various sizes – ZnO a NPs and ZnO b NPs – and we characterized the shedding ability of zinc ions within culture medium and the cytoplasm. We found that reactive oxygen species played a crucial role in ZnO NP-induced cytotoxicity, likely because zinc ions were leached from ZnO NPs. Apoptosis and cytoskeleton changes were also toxic responses induced by the ZnO NPs, and ZnO b NPs induced more significant toxic responses than ZnO a NPs in SHSY5Y cells. In conclusion, ZnO NPs induced toxic responses in SHSY5Y cells in a size-dependent manner, which can probably be attributed to their ion-shedding ability.

Porous tantalum (Ta) implants are highly corrosion resistant and biocompatible, and they possess significantly better initial stability than that of conventional titanium (Ti) implants. During loading wear, Ta nanoparticles (Ta-NPs) that were deposited on the surface of a porous Ta implant are inevitably released and come into direct contact with peri-implant osteoblasts. The wear debris may influence cell behavior and implant stabilization. However, the interaction of Ta-NPs with osteoblasts has not been clearly investigated. This study aimed to investigate the effect of Ta-NPs on cell proliferation and their underlying mechanism. The Cell Counting Kit-8 (CCK-8) assay was used to measure the cell viability of MC3T3-E1 mouse osteoblasts and showed that Ta-NP treatment could increase cell viability. Then, confocal microscopy, Western blotting, and transmission electron microscopy were used to confirm the autophagy induced by Ta-NPs, and evidence of autophagy induction was observed as positive LC3 puncta, high-LC3-II expression, and autophagic vesicle ultrastructures. The CCK-8 assay revealed that the cell viability was further increased and decreased by the application of an autophagy inducer and inhibitor, respectively. In addition, pre-treatment with autophagy inhibitor 3-methyladenine (3-MA) inhibited the Ta-NP-induced autophagy. These results indicate that the Ta-NPs can promote cell proliferation, that an autophagy inducer can further strengthen this effect and that an autophagy inhibitor can weaken this effect. In conclusion, autophagy was involved in Ta-NP-induced cell proliferation and had a promoting effect.

Proinflammatory responses are important aspects of the immune response to biomaterials, which may cause peri-implantitis and implant shedding. The purpose of this study was to test the cytotoxicity and proinflammatory effects of dicalcium silicate particles on RAW 264.7 macrophages and to investigate the proinflammatory response mechanism induced by C2S and tricalcium phosphate (TCP). C2S and TCP particles were characterized using scanning electron microscopy (SEM), energy spectrum analysis (EDS) and X-ray diffraction (XRD). Cytotoxicity and apoptosis assays with C2S and TCP in the murine RAW 264.7 cell line were tested using the cell counting kit-8 (CCK-8) assay and flow cytometry (FCM). The detection results showed that C2S and TCP particles had no obvious toxicity in RAW 264.7 cells and did not cause obvious apoptosis, although they both caused an oxidative stress response by producing ROS when the concentrations were at 100 μg/mL. C2S particles are likely to induce a proinflammatory response by inducing high TLR2, TNF-α mRNA, TNF-α proinflammatory cytokine, p-IκB, and p-JNK1 + JNK2 + JNK3 expression levels. When we added siRNA-TLR2-1, a significant reduction was observed. These findings support the theory that C2S particles induce proinflammatory responses through the TLR2-mediated NF-κB and JNK pathways in the murine RAW 264.7 macrophage cell line.

Among C2S-induced differentially expressed circRNAs, circ_1983 is involved in osteogenesis via circ_1983–miR-6931–Gas7 ceRNA interaction-mediated Runx2 upregulation.

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