Effects of adjacent periodontitis on osseointegrated dental implants.

PURPOSE: This study aimed to investigate whether new-onset periodontitis or apical periodontitis in the adjacent teeth affects osseointegrated dental implants in a beagle dog model. METHODS: One control group and 2 experimental groups (periodontitis and apical periodontitis groups) were defined based on the presence of experimental periodontitis or apical periodontitis, with 1 beagle dog randomly assigned to each group. The mandibular second and fourth premolars on both sides of the 3 beagles were extracted. Eight weeks after extraction, 4 bone-level implant fixtures, 2 on both sides of each mandible, were placed in each beagle. Six weeks after implant surgery, healing abutments were connected. After sufficient osseointegration, plaque control was performed in the control group, while periodontitis and apical periodontitis were induced in the experimental groups. The beagles were euthanized for histological analyses 20 weeks after induction of experimental periodontitis. Statistical analyses were performed using the Kruskal-Wallis test with the Bonferroni correction to compare the 3 groups. RESULTS: The implants in the control and apical periodontitis groups were well-maintained, while those in the periodontitis group showed clinical signs of inflammation with bone resorption. The bone-to-implant contact (BIC) and bone area values in the periodontitis group were lower than those in the other groups. The distance between the implant shoulder and the first BIC was significantly greater in the periodontitis group than in the control group (P<0.05). CONCLUSIONS: The presence of periodontitis in adjacent teeth can pose a risk to dental implants, potentially resulting in peri-implantitis. However, this was not observed for apical periodontitis. Within the limitations of this study, periodontal care is necessary to reduce the impact of periodontitis in adjacent teeth on osseointegrated implants.

Dental-derived cells for regenerative medicine: stem cells, cell reprogramming, and transdifferentiation.

Embryonic stem cells have been a popular research topic in regenerative medicine owing to their pluripotency and applicability. However, due to the difficulty in harvesting them and their low yield efficiency, advanced cell reprogramming technology has been introduced as an alternative. Dental stem cells have entered the spotlight due to their regenerative potential and their ability to be obtained from biological waste generated after dental treatment. Cell reprogramming, a process of reverting mature somatic cells into stem cells, and transdifferentiation, a direct conversion between different cell types without induction of a pluripotent state, have helped overcome the shortcomings of stem cells and raised interest in their regenerative potential. Furthermore, the potential of these cells to return to their original cell types due to their epigenetic memory has reinforced the need to control the epigenetic background for successful management of cellular differentiation. Herein, we discuss all available sources of dental stem cells, the procedures used to obtain these cells, and their ability to differentiate into the desired cells. We also introduce the concepts of cell reprogramming and transdifferentiation in terms of genetics and epigenetics, including DNA methylation, histone modification, and non-coding RNA. Finally, we discuss a novel therapeutic avenue for using dental-derived cells as stem cells, and explain cell reprogramming and transdifferentiation, which are used in regenerative medicine and tissue engineering.

The healing pattern of a 4 mm proximal infrabony defect was not significantly different from a 2 mm defect adjacent to dental implant in a canine mandible.

PURPOSE: The purpose of this study was to evaluate and compare the healing patterns of 2-mm and 4-mm proximal infrabony defects adjacent to dental implants in canine mandibles. METHODS: Four male beagles were used. Two groups were created: a 2-mm group (n=4) and a 4-mm group (n=4) depending on the horizontal dimension of proximal infrabony defects adjacent to implants. Bone healing patterns between the 2 groups were evaluated and compared at 8 and 16 weeks using radiographic, histological, histomorphometric, and fluorescent labelling analyses. RESULTS: According to microcomputed tomography, the median bone volume fraction, bone mineral density, and the percentage of radiographic distance from the defect bottom to the most coronal bone-to-implant contact (radio-mcBIC) were 32.9%, 0.6 g/cm3, and 73.7% (8 weeks) and 45.7%, 0.7 g/cm3, and 76.0% (16 weeks) in the 2-mm group and 57.7%, 0.8 g/cm3, and 75.7% (8 weeks) and 50.9%, 0.8 g/cm3, and 74.7% (16 weeks) in the 4-mm group, respectively. According to histomorphometry, the median bone area fraction, mcBIC and the percentage of BIC amounted to 36.7%, 3.4 mm, and 58.4% (8 weeks) and 49.2%, 3.4 mm, and 70.2% (16 weeks) in the 2-mm group and 50.0%, 3.0 mm, and 64.8% (8 weeks) and 55.7%, 3.0 mm, and 69.6% (16 weeks) in the 4-mm group, respectively. No statistically significant differences were found between the groups for any variables (P>0.05). CONCLUSIONS: The proximal defects that measured 2 mm and 4 mm showed similar healing patterns at 8 and 16 weeks, and the top of bone formation in the defects was substantially limited to a maximum of 1.6 mm below the implant shoulder in both groups.

Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells.

Blood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial cells (EC)-derived sEVs (EC-sEVs) under atheroprotective laminar shear stress (LSS) and atheroprone low-oscillatory shear stress (OSS) and conducted a network analysis to identify the main biological processes modulated by sEVs' miRNAs. The EC-sEVs were collected from culture media of human umbilical vein endothelial cells exposed to atheroprotective LSS (20 dyne/cm2) and atheroprone OSS (±5 dyne/cm2). We explored the miRNA profiles in FSS-induced EC-sEVs (LSS-sEVs and OSS-sEVs) and conducted a network analysis to identify the main biological processes modulated by sEVs' miRNAs. In vivo studies were performed in a mouse model of partial carotid ligation. The sEVs' miRNAs-targeted genes were enriched for endothelial activation such as angiogenesis, cell migration, and vascular inflammation. OSS-sEVs promoted tube formation, cell migration, monocyte adhesion, and apoptosis, and upregulated the expression of proteins that stimulate these biological processes. FSS-induced EC-sEVs had the same effects on endothelial mechanotransduction signaling as direct stimulation by FSS. In vivo studies showed that LSS-sEVs reduced the expression of pro-inflammatory genes, whereas OSS-sEVs had the opposite effect. Understanding the landscape of EC-exosomal miRNAs regulated by differential FSS patterns, this research establishes their biological functions on a system level and provides a platform for modulating the overall phenotypic effects of sEVs.

Long-Term Human Histologic Evaluation of Sinus Bone Augmentation and Simultaneous Implant Placement.

This study aimed to histologically and histomorphometrically evaluate osseointegration following simultaneous implant placement and maxillary sinus augmentation. Three retrospective human cases are described in which implants were placed at the maxillary sinus site augmented with deproteinized bovine bone mineral (DBBM) and later retrieved due to implant fracture after 5 to 8 years of occlusal loading. The removed implants with bone were processed for histologic evaluation, and bone-to-implant contact (BIC), bone area (BA), and mirror-image bone area (MIBA) were measured. Mature lamella bone was mainly observed, and some unabsorbed grafted bone particles remained in all cases. The measured values of BIC, BA, and MIBA in the three consecutive threads with the highest values were 86.0% to 91.2%, 65.8% to 91.9%, and 73.0% to 90.4%, respectively, and there were no signs of inflammation. Within the limits of this study, these cases demonstrate successful bone formation after maxillary sinus bone augmentation with DBBM and simultaneous implant placement.

Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Protect Cardiomyocytes from Doxorubicin-Induced Cardiomyopathy by Upregulating Survivin Expression via the miR-199a-3p-Akt-Sp1/p53 Signaling Pathway.

Cardiotoxicity is associated with the long-term clinical application of doxorubicin (DOX) in cancer patients. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) including exosomes have been suggested for the treatment of various diseases, including ischemic diseases. However, the effects and functional mechanism of MSC-sEVs in DOX-induced cardiomyopathy have not been clarified. Here, MSC-sEVs were isolated from murine embryonic mesenchymal progenitor cell (C3H/10T1/2) culture media, using ultrafiltration. H9c2 cardiac myoblast cells were pretreated with MSC-sEVs and then exposed to DOX. For in vivo studies, male C57BL/6 mice were administered MSC-sEVs intravenously, prior to a single dose of DOX (15 mg/kg, intraperitoneal). The mice were sacrificed 14 days after DOX treatment. The results showed that MSC-sEVs protected cardiomyocytes from DOX-induced cell death. H9c2 cells treated with DOX showed downregulation of both phosphorylated Akt and survivin, whereas the treatment of MSC-sEVs recovered expression, indicating their anti-apoptotic effects. Three microRNAs (miRNAs) (miR 199a-3p, miR 424-5p, and miR 21-5p) in MSC-sEVs regulated the Akt-Sp1/p53 signaling pathway in cardiomyocytes. Among them, miR 199a-3p was involved in regulating survivin expression, which correlated with the anti-apoptotic effects of MSC-sEVs. In in vivo studies, the echocardiographic results showed that the group treated with MSC-sEVs recovered from DOX-induced cardiomyopathy, showing improvement of both the left ventricle fraction and ejection fraction. MSC-sEVs treatment also increased both survivin and B-cell lymphoma 2 expression in heart tissue compared to the DOX group. Our results demonstrate that MSC-sEVs have protective effects against DOX-induced cardiomyopathy by upregulating survivin expression, which is mediated by the regulation of Akt activation by miRNAs in MSC-sEVs. Thus, MSC-sEVs may be a novel therapy for the prevention of DOX-induced cardiomyopathy.

Safety evaluation of atmospheric pressure plasma jets in in vitro and in vivo experiments.

PURPOSE: The atmospheric pressure plasma jet (APPJ) has been introduced as an effective disinfection method for titanium surfaces due to their massive radical generation at low temperatures. Helium (He) has been widely applied as a discharge gas in APPJ due to its bactericidal effects and was proven to be effective in our previous study. This study aimed to evaluate the safety and effects of He-APPJ application at both the cell and tissue levels. METHODS: Cellular-level responses were examined using human gingival fibroblasts and osteoblasts (MC3T3-E1 cells). He-APPJ was administered to the cells in the experimental group, while the control group received only He-gas treatment. Immediate cell responses and recovery after He-APPJ treatment were examined in both cell groups. The effect of He-APPJ on osteogenic differentiation was evaluated via an alkaline phosphatase activity assay. In vivo, He-APPJ treatment was administered to rat calvarial bone and the adjacent periosteum, and samples were harvested for histological examination. RESULTS: He-APPJ treatment for 5 minutes induced irreversible effects in both human gingival fibroblasts and osteoblasts in vitro. Immediate cell detachment of human gingival fibroblasts and osteoblasts was shown regardless of treatment time. However, the detached areas in the groups treated for 1 or 3 minutes were completely repopulated within 7 days. Alkaline phosphatase activity was not influenced by 1 or 3 minutes of plasma treatment, but was significantly lower in the 5 minute-treated group (P=0.002). In vivo, He-APPJ treatment was administered to rat calvaria and periosteum for 1 or 3 minutes. No pathogenic changes occurred at 7 days after He-APPJ treatment in the He-APPJ-treated group compared to the control group (He gas only). CONCLUSIONS: Direct He-APPJ treatment for up to 3 minutes showed no harmful effects at either the cell or tissue level.

Periodontal Wound Healing and Tissue Regeneration: A Narrative Review.

Periodontal disease is a major public health issue, and various periodontal therapies have been performed to regenerate periodontal tissues. The periodontium is a complex structure composed of specialized tissues that support the teeth, and most periodontal surgeries are invasive procedures, including a resection of the gingiva or the alveolar bone. The periodontal wound healing process is slightly different from cutaneous wound healing and is similar to fetal healing, being almost scar-free. The aim of this review article is to provide an overview of periodontal wound healing and discuss various surgical and pharmaceutical approaches to achieve stable wound healing and improve the treatment outcomes. In addition, detrimental and limiting factors that induce a compromised prognosis are discussed, along with the perspective and future direction for successful periodontal tissue regeneration.

In ovariectomy-induced osteoporotic rat models, BMP-2 substantially reversed an impaired alveolar bone regeneration whereas PDGF-BB failed.

OBJECTIVES: We previously suggested an ovariectomy (OVX)-induced osteoporotic rat model showing an impaired alveolar bone defect healing. This study aimed to evaluate and compare the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on alveolar bone defect healing in OVX-induced osteoporotic rats. MATERIALS AND METHODS: A total of forty-one female rats were divided into four groups: a collagen group (n=10), a PDGF-BB group (n=11), a BMP-2 group (n=10), and a control group (n=10). Four months after OVX, alveolar bone drill-hole defects were created and grafted with collagen gel, rhPDGF-BB/collagen gel, or rhBMP-2/collagen gel. The defects in the control group were not grafted with any material. Defect healing was evaluated by histological, histomorphometric, and microcomputed tomographic (micro-CT) analyses at 2 and 4 weeks. RESULTS: According to the micro-CT analysis, the BMP-2 group exhibited the greatest bone volume fraction among all groups, while the PDGF-BB group did not show significant differences compared with the collagen group. The histomorphometric analysis showed a significantly larger amount of new bone area in the BMP-2 group than in the control and collagen groups at 4 weeks; however, the PDGF-BB group did not reach significant superiority compared with the other groups. CONCLUSIONS: Alveolar bone regeneration was significantly enhanced by the local use of rhBMP-2/collagen gel compared with the use of rhPDGF-BB/collagen gel in OVX-induced osteoporotic rats. CLINICAL RELEVANCE: A treatment modality using rhBMP-2 may be a promising approach to promote alveolar bone regeneration in patients suffering from postmenopausal osteoporosis.

Current advances of epigenetics in periodontology from ENCODE project: a review and future perspectives.

BACKGROUND: The Encyclopedia of DNA Elements (ENCODE) project has advanced our knowledge of the functional elements in the genome and epigenome. The aim of this article was to provide the comprehension about current research trends from ENCODE project and establish the link between epigenetics and periodontal diseases based on epigenome studies and seek the future direction. MAIN BODY: Global epigenome research projects have emphasized the importance of epigenetic research for understanding human health and disease, and current international consortia show an improved interest in the importance of oral health with systemic health. The epigenetic studies in dental field have been mainly conducted in periodontology and have focused on DNA methylation analysis. Advances in sequencing technology have broadened the target for epigenetic studies from specific genes to genome-wide analyses. CONCLUSIONS: In line with global research trends, further extended and advanced epigenetic studies would provide crucial information for the realization of comprehensive dental medicine and expand the scope of ongoing large-scale research projects.

Comparison of Periodontopathic Bacterial Profiles of Different Periodontal Disease Severity Using Multiplex Real-Time Polymerase Chain Reaction.

Periodontopathic bacteria are known to have a pivotal role in the pathogenesis of periodontitis. The aim of the study was to quantitatively compare bacterial profile of patients with different severity of periodontal disease using samples from mouthwash and the subgingival area. Further analysis was performed to evaluate the correlation between mouthwash and two subgingival sampling methods: paperpoint and gingival retraction cord; 114 subjects enrolled in the study, and were divided equally into three groups according to disease severity. Mouthwash and subgingival sampling were conducted, and the samples were quantitatively analyzed for 11 target periodontopathic bacteria using multiplex real-time PCR. There were statistically significant differences in bacterial counts and prevalence of several species between the study groups. Mouthwash sampling showed significant correlations with two different subgingival sampling methods in regard to the detection of several bacteria (e.g., ρ = 0.793 for Porphyromonas gingivalis in severe periodontitis), implying that mouthwash sampling can reflect subgingival microbiota. However, the correlation was more prominent as disease severity increased. Although bacteria in mouthwash have potential to become a biomarker, it may be more suitable for the diagnosis of severe periodontitis, rather than early diagnosis. Further research is required for the discovery of biomarkers for early diagnosis of periodontitis.

Periodontal Regeneration Using Recombinant Human Bone Morphogenetic Protein-2 and a Bilayer Collagen Matrix.

Previous studies demonstrated that recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered using a collagen sponge could be a candidate for periodontal regeneration therapy. However, there is little evidence related to rhBMP-2 delivered with a bilayer collagen matrix. The aim of this study was to investigate the proper dose of rhBMP-2 using a bilayer collagen matrix for periodontal regeneration in a 1-wall defect. The mandibular first premolars and first molars of 6 beagle dogs were extracted, and an 8-week healing period was allowed. One-wall intrabony defects (4 mm in width and 5 mm in height) were made on the mesial side of the 2nd premolar and/or the distal side of the 4th premolar bilaterally. Subsequently, a bilayer collagen matrix containing 0 µg (C), 200 µg (T1), or 500 µg (T2) of lyophilized rhBMP-2 was randomly applied to the defect area. Calcein and xylenol orange were injected at 4 and 8 weeks following the surgery, respectively, to label periodic bone formation. After a 12-week healing period, the animals were sacrificed for micro-computed tomography and histomorphometric analysis. Bone mineral density and bone volume density showed statistically significant differences between the control group and group T1, while no significant differences were observed between the control group and group T2 or between groups T1 and T2. The bone height in groups T1 and T2 was smaller than that in the control group. Low doses of rhBMP-2 delivered using a bilayer collagen matrix in 1-wall intrabony defects can promote periodontal regeneration compared to no or high doses of rhBMP-2.

Comparison of experimental peri-implantitis models after application of ex vivo BMP2 gene therapy using periodontal ligament stem cells.

Peri-implantitis is an inflammatory disease that results in bone destruction around dental implants. A preclinical study using beagle models is frequently performed prior to clinical application in dentistry. Previously, we proposed an immediate peri-implantitis experimental model with a shorter experimental duration and less expense than the conventional experimental model. However, the differences in the regenerative outcomes between the immediate and conventional models were not fully revealed. In this study, we aimed to compare the regenerative outcomes between both models when ex vivo BMP2 gene therapy using autologous periodontal ligament stem cells (B2/PDLSCs) was applied to peri-implantitis defects. The results showed that the defect depths were significantly different between both models. New bone formation occurred in both models, but there were significant differences between the models. More than 70% of the defects were filled with newly formed bone in the conventional model, whereas 30-40% of the defects were filled in the immediate model. However, after adjustment for the differences in the defect depths between the models, the statistically significant differences in the regenerative outcomes between the models were lost. In conclusion, the inferior regenerative outcome of an immediate peri-implantitis model at B2/PDLSCs transplantation resulted from the defect depths, not the model itself.

Ovariectomy and timing of impaired maxillary alveolar bone regeneration: An experimental study in rats.

BACKGROUND: The aim of this study was to seek the critical time for impairment of alveolar bone regeneration after ovariectomy (OVX) in rats. METHODS: A total of 32 female rats were used. Test group rats were divided into a 2M group (n = 8), a 3M group (n = 8) and a 4M group (n = 8) according to the duration from OVX to defect creation. Bilateral OVX was performed in all test groups, and a sham operation was performed in the control group (n = 8). Drill-hole defects (1.5 mm diameter, 2 mm length) were created on both sides of the maxilla. All rats were euthanized 2 and 4 weeks after the surgery. Microcomputed tomographic (micro-CT), histological, and histomorphometric analyses and in vitro experiments were performed. RESULTS: The 4M group showed significantly less new bone formation and a lower bone mineral density than the other groups in the micro-CT analysis. The histomorphometric analysis also revealed that the 4M group showed significantly less new bone formation than the control and 2M groups. The rats in the 4M group showed significantly higher alkaline phosphatase expression levels and a larger number of calcified nodules than rats in the other groups, whereas osteoclastic activity was significantly lower in the 4M group than in the other groups. CONCLUSIONS: The critical time for impairment of alveolar bone regeneration was 4 months after OVX in rats.

Bone regeneration into side openings and hollow inner channel of a dental implant.

The current study examined whether bone can regenerate into an open space fabricated inside the metal implant and maintain its quantity and quality at the early post-implantation healing periods. 12 conventional one piece screw type titanium dental implants (control group) and 12 hybrid dental implants with spiral side openings (0.58 mm wide) connected to hollow inner channel (experimental group) were bilaterally placed in each quadrant at the P3, P4 and M1 positions in mandible of 4 adult beagles following 2 months of post-extraction healing. Fluorescent bone labels to qualitatively evaluate newly formed bone tissues were administered at 2 and 4 weeks of post-implantation periods, respectively. 3 control and 3 experimental bone-implant constructs for each animal were dissected from 2 animals at each 3 and 6 weeks of post-implantation healing periods. Undecalcified specimens were prepared from each construct for histological analyses to measure bone-to-implant contact (BIC) and interfacial bone area (BA), and also for nanoindentation and scanning electron microscopy to assess elastic modulus (E) and composition of bone tissues surrounding the implants, respectively. A substantial amount of newly formed bone tissues were observed at the implant interfaces of both implant groups. Bone tissues successfully regenerate through the side openings and hollow inner channel of the experimental implant as early as 3 weeks of post-implantation healing. The E values of the newly formed bone tissues were measured comparable to those of normal bone tissues. The current results indicate that the new hybrid implant can conduct bone regeneration into the inner architecture, which likely improves stability of the implant system by enhancing integrity of implant with interfacial bone.

A retrospective study of implants placed following 1-stage or 2-stage maxillary sinus floor augmentation by the lateral window technique performed on residual bone of <4 mm: Results up to 10 years of follow-up.

BACKGROUND: The purpose of this study was to compare the survival rates of implants placed following 1-stage or 2-stage maxillary sinus floor augmentation by the lateral window technique (SFALW) performed on residual bone of <4 mm. METHODS: This study was conducted based on dental records and radiographs obtained from patients who received SFALW from March 2006 to June 2014, being followed up between March 2006 and December 2017. They were divided into 1-stage and 2-stage groups according to the SFALW performed. Statistical analysis was performed to evaluate whether a significant difference existed between 1-stage and 2-stage SFALW in terms of survival rates. Multivariable logistic regression analysis was used to examine the influence of multiple variables on implant failure. RESULTS: A total of 395 implants (156 implants in the 1-stage group, 239 implants in the 2-stage group) in 167 patients fulfilled the inclusion criteria. Among them, 13 implants (five implants in the 1-stage group, eight implants in the 2-stage group) failed. No significant difference was found in the 10-year cumulative survival rate of implants between the 1-stage group and the 2-stage group (96.8% and 92.5%, respectively, P = 0.656). Multivariable logistic regression analysis demonstrated that implant failure was significantly influenced by implant length and functional time following prosthetic loading. CONCLUSIONS: The 10-year cumulative survival rates showed no statistically significant difference between implants following 1-stage and 2-stage maxillary SFALW performed on residual bone height of <4 mm.

The bactericidal effect of an atmospheric-pressure plasma jet on Porphyromonas gingivalis biofilms on sandblasted and acid-etched titanium discs.

PURPOSE: Direct application of atmospheric-pressure plasma jets (APPJs) has been established as an effective method of microbial decontamination. This study aimed to investigate the bactericidal effect of direct application of an APPJ using helium gas (He-APPJ) on Porphyromonas gingivalis biofilms on sandblasted and acid-etched (SLA) titanium discs. METHODS: On the SLA discs covered by P. gingivalis biofilms, an APPJ with helium (He) as a discharge gas was applied at 3 different time intervals (0, 3, and 5 minutes). To evaluate the effect of the plasma itself, the He gas-only group was used as the control group. The bactericidal effect of the He-APPJ was determined by the number of colony-forming units. Bacterial viability was observed by confocal laser scanning microscopy (CLSM), and bacterial morphology was examined by scanning electron microscopy (SEM). RESULTS: As the plasma treatment time increased, the amount of P. gingivalis decreased, and the difference was statistically significant. In the SEM images, compared to the control group, the bacterial biofilm structure on SLA discs treated by the He-APPJ for more than 3 minutes was destroyed. In addition, the CLSM images showed consistent results. Even in sites distant from the area of direct He-APPJ exposure, decontamination effects were observed in both SEM and CLSM images. CONCLUSIONS: He-APPJ application was effective in removing P. gingivalis biofilm on SLA titanium discs in an in vitro experiment.

Coxsackievirus and adenovirus receptor mediates the responses of endothelial cells to fluid shear stress.

Endothelial mechanotransduction by fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology through mechanosensors on the cell membrane. The coxsackievirus and adenovirus receptor (CAR) is not only a viral receptor but also a component of tight junctions and plays an important role in tissue homeostasis. Here, we demonstrate the expression, regulatory mechanism, and role of CAR in vascular endothelial cells (ECs) under FSS conditions. Disturbed flow increased, whereas unidirectional laminar shear stress (LSS) decreased, CAR expression in ECs through the Krüppel-like factor 2 (KLF2)/activator protein 1 (AP-1) axis. Deletion of CAR reduced the expression of proinflammatory genes and endothelial inflammation induced by disturbed flow via the suppression of NF-κB activation. Consistently, disturbed flow-induced atherosclerosis was reduced in EC-specific CAR KO mice. CAR was found to be involved in endothelial mechanotransduction through the regulation of platelet endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation. Our results demonstrate that endothelial CAR is regulated by FSS and that this regulated CAR acts as an important modulator of endothelial mechanotransduction by FSS.

BMP-2 Gene Delivery-Based Bone Regeneration in Dentistry.

Bone morphogenetic protein-2 (BMP-2) is a potent growth factor affecting bone formation. While recombinant human BMP-2 (rhBMP-2) has been commercially available in cases of non-union fracture and spinal fusion in orthopaedics, it has also been applied to improve bone regeneration in challenging cases requiring dental implant treatment. However, complications related to an initially high dosage for maintaining an effective physiological concentration at the defect site have been reported, although an effective and safe rhBMP-2 dosage for bone regeneration has not yet been determined. In contrast to protein delivery, BMP-2 gene transfer into the defect site induces BMP-2 synthesis in vivo and leads to secretion for weeks to months, depending on the vector, at a concentration of nanograms per milliliter. BMP-2 gene delivery is advantageous for bone wound healing process in terms of dosage and duration. However, safety concerns related to viral vectors are one of the hurdles that need to be overcome for gene delivery to be used in clinical practice. Recently, commercially available gene therapy has been introduced in orthopedics, and clinical trials in dentistry have been ongoing. This review examines the application of BMP-2 gene therapy for bone regeneration in the oral and maxillofacial regions and discusses future perspectives of BMP-2 gene therapy in dentistry.

Recent Advances of Useful Cell Sources in the Periodontal Regeneration.

BACKGROUND: Periodontitis is an inflammatory disease that can result in destruction of the tooth attachment apparatus. Therefore, periodontal tissue regeneration is currently an important focus of research in the field. Approaches using stem cells and reprogrammed cells, such as induced pluripotent stem cells (iPSCs) or trans-differentiated cells, represent the cutting edge in periodontal regeneration, and have led to many trials for their clinical application. Objectives and Results: In this review, we consider all available stem cell sources, methods to obtain the cells, their capability to differentiate into the desired cells, and the extent of their utilization in periodontal regeneration. In addition, we introduce the new concepts of using iPSCs and transdifferentiated cells for periodontal regeneration. Finally, we discuss the promise of tissue engineering for improving cell therapy outcomes for periodontal regeneration. CONCLUSIONS: Despite their limitations, iPSCs and trans-differentiated cells may be promising cell sources for periodontal tissue regeneration. Further collaborative investigation is required for the effective and safe application of these cells in combination with tissue engineering elements, like scaffolds and biosignals.