Explore the vast range of titles available.

Orthodontic tooth movement relies on coordinated tissue resorption and formation in the surrounding bone and periodontal ligament. Tooth loading causes local hypoxia and fluid flow, initiating an aseptic inflammatory cascade culminating in osteoclast resorption in areas of compression and osteoblast deposition in areas of tension. Compression and tension are associated with particular signaling factors, establishing local gradients to regulate remodeling of the bone and periodontal ligament for tooth displacement. Key regulators of inflammation and tissue turnover include secreted factors like RANK ligand and osteoprotegerin, transcription factors such as RUNX2 and hypoxia-inducible factor, cytokines, prostaglandins, tissue necrosis factors, and proteases, among others. Inflammation occurred during tooth movement needs to be well controlled, as dysregulated inflammation leads to tissue destruction manifested in orthodontic-induced root resorption and periodontal disease. Understanding the biology has profound clinical implications especially in the area of accelerating orthodontic tooth movement. Surgical, pharmacological, and physical interventions are being tested to move teeth faster to reduce treatment times and time-dependent adverse outcomes. Future developments in acceleratory technology and custom appliances will allow orthodontic tooth movement to occur more efficiently and safely.

Polydopamine, a mussel-inspired self-adherent polymer of dopamine, has impressive adhesive properties and thus is one of the most versatile approaches to functionalize tissue engineering scaffolds. To date, many types of polydopamine-functionalized scaffolds have been manufactured and extensively applied in bone tissue engineering at the preclinical stage. However, how polydopamine is biodegraded and metabolized during the bone healing process and the side effects of its metabolite remain largely unknown. These issues are often neglected in the modern manufacture of polydopamine-functionalized materials and restrict them from stepping forward to clinical applications. In this study, using our bioinspired polydopamine-laced hydroxyapatite collagen calcium silicate material as a representative of polydopamine-functionalized tissue engineering scaffolds, we discovered that polydopamine can be metabolized to dopamine specifically by osteoclasts, which we termed “osteoclast-driven polydopamine-to-dopamine release”. The released dopamine showed an osteoinductive effect in vitro and promoted bone regeneration in calvarial critical-sized defects. The concept of “osteoclast-driven polydopamine-to-dopamine release” has considerable application potential. It could be easily adopted by other existing polydopamine-functionalized scaffolds: just by recruiting osteoclasts. Once adopted, scaffolds will obtain a dopamine-releasing function, which enables their modulation of osteoblast activity and hence elevates the osteoinductive effect. Thus, “osteoclast-driven polydopamine-to-dopamine release” serves as an upgrade patch, which is useful for many existing polydopamine-functionalized materials.

A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-associated molecular patterns. The activation of certain PRRs can lead to the assembly of macromolecular oligomers termed , which are responsible for pro-inflammatory cytokine maturation and secretion and thus activate host inflammatory responses. About 10 years ago, the absent in melanoma 2 (AIM2) was independently discovered by four research groups, and among the \"canonical\" inflammasomes [including AIM2, NLR family pyrin domain (NLRP)1, NLRP3, NLR family apoptosis inhibitory protein (NAIP)/NLR family, caspase activation and recruitment domain (CARD) containing (NLRC)4, and pyrin], AIM2 so far is the only one that simultaneously acts as a cytosolic DNA sensor due to its DNA-binding ability. Undoubtedly, such a double-faceted role gives AIM2 greater mission and more potential in the mediation of innate immune responses. Therefore, AIM2 has garnered much attention from the broad scientific community during its first 10 years of discovery (2009-2019). How the AIM2 inflammasome is related to oral diseases has aroused debate over the past few years and is under active investigation. AIM2 inflammasome may potentially be a key link between oral diseases and innate immunity. In this review, we highlight the current knowledge of the AIM2 inflammasome and its critical role in the pathogenesis of various oral diseases, which might offer future possibilities for disease prevention and targeted therapy utilizing this continued understanding.

Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5’ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3 −/− primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells. RNA viruses can be detected by immune cell pattern recognition receptors, such as RLRs, resulting in MAVS-TBK1-IRF3 signalling and production of antiviral type 1 interferons. Here the authors show that macrophage TRAF3-interacting protein 3 regulates this signalling pathway by interacting with TRAF3 and TBK1 to suppress interferon responses.

Genome-wide association studies (GWAS) have identified Optineurin ( OPTN ) as genetically linked to Paget’s disease of the bone (PDB), a chronic debilitating bone remodeling disorder characterized by localized areas of increased bone resorption and abnormal bone remodeling. However, only ~10% of mouse models with a mutation in Optn develop PDB, thus hindering the mechanistic understanding of the OPTN-PDB axis. Here, we reveal that 100% of aged Optn global knockout ( Optn − /− ) mice recapitulate the key clinical features observed in PDB patients, including polyostotic osteolytic lesions, mixed-phase lesions, and increased serum levels of alkaline phosphatase (ALP). Differentiation of primary osteoclasts ex vivo revealed that the absence of Optn resulted in an increased osteoclastogenesis. Mechanistically, Optn -deficient osteoclasts displayed a significantly decreased type I interferon (IFN) signature, resulting from both defective production of IFNβ and impaired signaling via the IFNα/βR, which acts as a negative feedback loop for osteoclastogenesis and survival. These data highlight the dual roles of OPTN in the type I IFN response to restrain osteoclast activation and bone resorption, offering a novel therapeutic target for PDB. Therefore, our study describes a novel and essential mouse model for PDB and define a key role for OPTN in osteoclast differentiation.

A hydroxyapatite-collagen (HC) composite material can mimic composition and ultra-structures of natural bone and provide adequate bioactive material-tissue interactions. Incorporation of dopamine (DA) is one of keys in increasing the mechanical strength of the HC material to approaching that of cortical bone. In this study, the in vitro osteogenic effects of polydopamine-laced hydroxyapatite collagen calcium silicate (HCCS-PDA) were examined by culturing rat mesenchymal stem cells (rMSCs) on HCCS-PDA and HCCS coated plates. HCCS-PDA group demonstrated less cytotoxic from Live/Dead cytotoxic assay and displayed higher cell attachment, proliferation and mineralization than the HCCS group in vitro . For in vivo bone regeneration, HCCS-PDA or HCCS particulates with or without rMSC aggregates were implanted into rat critical-sized calvarial defects (CSD). After 12 weeks, calvarial bone regeneration was evaluated radiographically, histologically, and histomorphometrically. While the majority of new bone formation occurred around the HCCS-PDA particulates with rMSC aggregates, The HCCS-PDA particulates without rMSC aggregates showed limited osteoconductivity. HCCS with or without rMSC aggregates resulted in less bone formation, indicating a prominent role of DA in effective bone regeneration. Therefore, the HCCS-PDA biomaterial with the aid of rMSCs can be used to develop therapeutic strategies in bone tissue engineering with numerable clinical applications.

Abnormally increased resorption contributes to bone degenerative diseases such as Paget’s disease of bone (PDB) through unclear mechanisms. Recently, the optineurin (OPTN) gene has been implicated in PDB, and global OPTN knockout mice ( Optn −/− ) were shown to exhibit increased formation of osteoclasts (osteoclastogenesis). Growing evidence, including our own, has demonstrated that intracellular reactive oxygen species (ROS) stimulated by receptor activator of nuclear factor kappa-B ligand (RANKL) can act as signaling molecules to promote osteoclastogenesis. Here, we report that OPTN interacts with nuclear factor erythroid-derived factor 2-related factor 2 (NRF2), the master regulator of the antioxidant response, defining a pathway through which RANKL-induced ROS could be regulated for osteoclastogenesis. In this study, monocytes from Optn −/− and wild-type ( Optn +/+ ) mice were utilized to differentiate into osteoclasts, and both qRT-PCR and tartrate-resistant acid phosphatase (TRAP) staining showed that the Optn −/− monocytes exhibited enhanced osteoclastogenesis compared to the Optn +/+ cells. CellROX ® staining, qRT-PCR, and Western blotting indicated that OPTN deficiency reduced the basal expression of Nrf2 , inhibited the expression of NRF2-responsive antioxidants, and increased basal and RANKL-induced intracellular ROS levels, leading to enhanced osteoclastogenesis. Coimmunoprecipitation (co-IP) showed direct interaction, and immunofluorescence staining showed perinuclear colocalization of the OPTN-NRF2 granular structures during differentiation. Finally, curcumin and the other NRF2 activators attenuated the hyperactive osteoclastogenesis induced by OPTN deficiency. Collectively, our findings reveal a novel OPTN-mediated mechanism for regulating the NRF2-mediated antioxidant response in osteoclasts and extend the therapeutic potential of OPTN in the aging process resulting from ROS-triggered oxidative stress, which is associated with PDB and many other degenerative diseases. Bone degeneration: Identifying a damage-limiting protein The protein optineurin is implicated in regulating the breakdown of bone during natural maintenance by a mechanism that may be relevant to understanding and treating degenerative bone diseases. Cells called osteoclasts mediate bone breakdown during natural bone turnover, but excessive breakdown occurs in some bone diseases. Working with cultured mouse cells, researchers in the USA, led by Ching-Chang Ko at Ohio State University, Columbus, and Henry Tseng at Duke University, identified a molecular signaling pathway in which optineurin interacts with a protein called NRF2, which is known as the master regulator of the antioxidant response. This interaction allows optineurin to limit the production of chemicals called reactive oxidative species which stimulate osteoclast generation. The findings suggest that drugs regulating the optineurin signaling pathway may help treat bone degeneration and possibly other degenerative diseases.

The objective of this study was to explore the feasibility of current 3D reconstruction in assessing the position of maxillary impacted canines from 2D panoramic X-rays. A dataset was created using pre-treatment CBCT data from a total of 123 patients, comprising 74 patients with impacted canines and 49 patients without impacted canines. From all 74 subjects, we generated a dataset containing paired 2D panoramic X-rays and pseudo-3D images. This pseudo-3D image contained information about the location of the impacted canine in the buccal/lingual, mesial/distal, and apical/coronal positions. These data were utilized to train a deep-learning reconstruction algorithm, a generative AI. The location of the crown of the maxillary impacted canine was determined based on the output of the algorithm. The reconstruction was evaluated using the structure similarity index measure (SSIM) as a metric to indicate the quality of the reconstruction. The prediction of the impacted canine’s location was assessed in both the mesiodistal and buccolingual directions. The reconstruction algorithm predicts the position of the impacted canine in the buccal, middle, or lingual position with 41% accuracy, while the mesial and distal positions are predicted with 55% accuracy. The mean SSIM for the output is 0.71, with a range of 0.63 to 0.84. Our study represents the first application of AI reconstruction output for multidisciplinary care involving orthodontists, periodontists, and maxillofacial surgeons in diagnosing and treating maxillary impacted canines. Further development of deep-learning algorithms is necessary to enhance the robustness of dental reconstruction applications.

White spot lesions (WSLs), a side effect of orthodontic treatment, can result in reversible and unaesthetic results. Graphene oxide (GO) with a bioactive glass (BAG) mixture (BAG@GO) was added to Low-Viscosity Transbond XT (LV) in a ratio of 1, 3, and 5%. The composite’s characterization and its physical and biological properties were verified with scanning electron microscopy (SEM) and X-ray diffraction (XRD); its microhardness, shear bond strength (SBS), cell viability, and adhesive remnant index (ARI) were also assessed. Efficiency in reducing WSL was evaluated using antibacterial activity of S. mutans. Anti-demineralization was analyzed using a cycle of the acid-base solution. Adhesives with 3 wt.% or 5 wt.% of BAG@GO showed significant increase in microhardness compared with LV. The sample and LV groups showed no significant differences in SBS or ARI. The cell viability test confirmed that none of the sample groups showed higher toxicity compared to the LV group. Antibacterial activity was higher in the 48-h group than in the 24 h group; the 48 h test showed that BAG@GO had a high antibacterial effect, which was more pronounced in 5 wt.% of BAG@GO. Anti-demineralization effect was higher in the BAG@GO-group than in the LV-group; the higher the BAG@GO concentration, the higher the anti-demineralization effect.

Multiple growth factors（e.g., BMP2, TGF-b1, FGF2） and isolated genes have been shown to improve osteoblastic proliferation and mineralization, advancing bone tissue engineering. Among these factors, both polydopamine（PDA） and dopamine（DA） monomer have recently been reported to increase osteoblast proliferation and mineralization in vitro. Although a well-characterized neurotransmitter, DA＇s role in the bone is unknown. We hypothesize that DA can directly act on osteoblasts, and examined whether osteoblasts express DA receptors that respond to exogenous DA. m RNAs and protein cell lysates were obtained from MC3T3-E1 cells during osteogenic differentiation phase. Reverse transcription polymerase chain reaction and western blot analysis were used to examine the expression of DA receptors, D1–D5. Dose-response effect and time course of DA treatment on cell proliferation, mineralization, and osteogenic differentiation were investigated at pre-determined days. Real-time PCR was performed to investigate whether DA affects osteogenic gene expression（ALP, BSP, OC, OSX, RUNX2, and Collagen1a2） with or without receptor antagonists（SCH233390 and GR103691）. Two-way ANOVA was used for statistical analysis. All five DA receptors（D1, D2, D3, D4, and D5） m RNAs and proteins were expressed in MC3T3-E1 cells. DA treatment increased cell proliferation for up to 7 days（P, 0.05）. Osteogenic mineralization was significantly greater in the DA-treated group than control group（P, 0.05）. Finally, expression of all the osteogenic genes was inhibited by DA receptor antagonists for D1, D3, and D5. Our findings suggest that MC3T3-E1 osteoblasts express functional DA receptors that enhance proliferation and mineralization. PDA is not biologically inert and has important implications in orthopedic applications. Furthermore, osteoblast differentiation might be regulated by the nervous system, presumably during bone development, remodeling, or repair.