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BACKGROUND: Bacterial-induced inflammation instigates the destruction of hard and soft tissues surrounding teeth in periodontitis. In severe cases, the increased number and activity of osteoclasts induces the resorption of alveolar bones, ultimately leading to tooth loss. Because of their diverse chemical structures and bioactivities, natural compounds are often suggested to treat a wide variety of diseases, including inflammatory disorders. METHODS: In the present study, we demonstrated an inhibitory effect of gossypetin, a hexahydroxy flavone, on osteoclast differentiation and bone resorption using in vitro culture of osteoclasts from mouse bone marrow macrophage (BMM) precursors and in vivo model of ligature-induced periodontitis in mice. RESULTS: Gossypetin significantly reduced the differentiation of osteoclasts from mouse BMM precursors in the presence of the receptor activator of nuclear factor κB ligand (RANKL). In vitro, gossypetin inhibited critical signaling events downstream of RANKL including the auto-amplification of nuclear factor of activated T-cells, cytoplasmic 1, Ca2+ oscillations, and the generation of reactive oxygen species. In a mouse ligature-induced periodontitis model, the administration of gossypetin significantly reduced osteoclastogenesis and alveolar bone resorption. Furthermore, gossypetin prevented the ligature-induced increase in macrophages and T cells and reduced the production of tumor necrosis factor-α and interleukin-6. CONCLUSION: Taken together, these results show anti-osteoclastogenic and anti-inflammatory effects of gossypetin, suggesting the potential use of this natural compound in periodontitis.
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Periodontitis is known to be affected by high-glucose conditions, which poses a challenge to periodontal tissue regeneration, particularly in bone formation. In this study, the potential effects of resveratrol (3,5,4'-trihydroxystilbene, RSV) in facilitating bone formation under high-glucose conditions after periodontitis has been investigated. We focused on the analysis of osteoblasts and periodontal ligament cells, which are essential for bone formation including cell proliferation and differentiation. And we aimed to investigate the impact of RSV on bone healing, employed diabetic mouse model induced by streptozotocin and confirmed through histological observation. High-glucose conditions adversely affected cell proliferation and ALP activity in both MC3T3-E1 and hPDLF in vitro, with more significant impact on MC3T3-E1 cells. RSV under high-glucose conditions had positive effects on both, showing early-stage effects for MC3T3-E1 cells and later-stage effects for hPDLF cells. RSV seemed to have a more pronounced rescuing role in MC3T3-E1 cells. Increased ALP activity was observed and the expression levels of significant genes, such as Col 1, TGF-ß1, ALP, and OC, in osteogenic differentiation were exhibited stage-specific expression patterns. Upregulated Col 1 and TGF-ß1 were detected in the early stage, and then ALP and OC expressions became more pronounced in the later stages. Similarly, stronger positive reactions against RUNX2 were detected in the RSV-treated group compared to the control. Furthermore, in in vivo experiment, RSV stimulates the growth and differentiation of osteoblasts, thereby promoting bone formation. High-glucose levels have the potential to impair cellular functions and the regenerative capacity to facilitate bone formation with MC3T3-E1 rather than hPDLF cells. Resveratrol appears to facilitate the inherent abilities of MC3T3-E1 cells compared with hPDLF cells, indicating its potential capacity to restore functionality during periodontal regeneration.
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OBJECTIVE AND BACKGROUND: This research aimed to examine the role of C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 8 (CXCL8; also known as IL-8) in neutrophilic inflammation triggered by peri-implantitis and to shed light on the underlying mechanisms that link them to the development of this condition. MATERIALS: This study included 40 patients who visited the Department of Periodontology at Kyungpook University Dental Hospital. They were divided into two groups based on their condition: healthy implant (HI) group (n = 20) and peri-implantitis (PI) group (n = 20). Biopsy samples of PI tissue were collected from the patients under local anesthesia. HI tissue was obtained using the same method during the second implant surgery. To construct libraries for control and test RNAs, the QuantSeq 3' mRNA-Seq Library Prep Kit (Lexogen, Inc., Austria) was used according to the manufacturer's instructions. Samples were pooled based on representative cytokines obtained from RNA sequencing results and subjected to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Hematoxylin and eosin staining, and immunohistochemistry (IHC) analysis were performed to visually assess expression levels and analyze tissue histology. Student's t-test was employed to conduct statistical analyses. RESULTS: Initially, heatmaps were used to examine gene expression variations between the HI and PI groups based on the results of RNA sequencing. Notably, among various cytokines, CXCL5 and CXCL8 had the highest expression levels in the PI group compared with the HI group, and they are known to be associated with inflammatory responses. In the gingival tissues, the expression of genes encoding cytokines such as interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and CXCL5/CXCL8 was assessed via RT-qPCR. The mRNA expression level of CXCL5/CXCL8 significantly increased in the PI group compared with the HI group (p < .045). Contrarily, the mRNA expression level of interleukin 36 receptor antagonist (IL36RN) significantly decreased (p < .008). IHC enabled examination of the distribution and intensity of CXCL5/CXCL8 protein expression within the tissue samples. Specifically, increased levels of CXCL5/CXCL8 promote inflammatory responses, cellular proliferation, migration, and invasion within the peri-implant tissues. These effects are mediated through the activation of the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: This study found that the PI sites had higher gene expression level of CXCL8/CXCL5 in the soft tissue than HI sites, which could help achieve more accurate diagnosis and treatment planning.
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Quimiocina CXCL5 , Interleucina-8 , Neutrófilos , Periimplantitis , Humanos , Periimplantitis/patología , Periimplantitis/inmunología , Periimplantitis/metabolismo , Interleucina-8/análisis , Masculino , Neutrófilos/patología , Femenino , Persona de Mediana Edad , Inflamación , AdultoRESUMEN
Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced ß-catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild-type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.
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Oral squamous cell carcinoma (OSCC) is a prevalent oral and maxillofacial cancer with high mortality as OSCC cells readily invade tissues and metastasize to cervical lymph nodes. Although imatinib exhibits potential anticancer and remarkable clinical activities that therapeutically affect several cancer types, its specific impact on OSCC has yet to be fully explored. Therefore, this study investigated the potential anticancer effect of imatinib on OSCC cells and the underlying mechanisms. The Cell Counting Kit-8 was used to determine the impact of imatinib on cell viability. Then, morphological cell proliferation analysis was conducted to examine how imatinib impacted OSCC cell growth. Moreover, OSCC cell migration was determined through wound-healing assays, and colony formation abilities were investigated through the soft agar assay. Lastly, the effect of imatinib on OSCC cell apoptosis was verified with flow cytometry, and its inhibitory mechanism was confirmed through Western blot. Our results demonstrate that imatinib effectively inhibited OSCC cell proliferation and significantly curtailed OSCC cell viability in a time- and concentration-dependent manner. Furthermore, imatinib suppressed migration and colony formation while promoting OSCC cell apoptosis by enhancing p53, Bax, and PARP expression levels and reducing Bcl-2 expression. Imatinib also inhibited the PI3K/AKT/mTOR signaling pathway and induced OSCC cell apoptosis, demonstrating the potential of imatinib as a treatment for oral cancer.
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The oral colonization of periodontal pathogens onto gingival tissues establishes hypoxic microenvironment, often disrupting periodontal homeostasis in conjunction with oxidative stress. The association between reactive oxygen species (ROS) and osteolytic periodontitis have been suggested by recent studies. PTEN-induced kinase 1 (PINK1), a mitochondrial serine/threonine kinase, is an essential protein for mitochondrial quality control as it protects cells from oxidative stress by promoting degradation of damaged mitochondria through mitophagy. However, the pathophysiological roles of PINK1 in osteoclast-mediated bone loss have not been explored. Here we aimed to determine whether PINK1 plays a role in the regulation of osteoclastogenesis and alveolar bone resorption associated with periodontitis. C57BL/6 wild type (WT) and Pink1 knockout (KO) mice were subjected to ligature-induced periodontitis (LIP), and alveolar bones were evaluated by µCT-analysis and tartrate-resistant acid phosphatase (TRAP) staining. The µCT-analysis showed that bone volume fraction and travecular thickness were lower in Pink1 KO compared to WT mice. The number of TRAP-positive osteoclasts was markedly increased in the periodontal tissues of Pink1 KO mice with LIP. The genetic silencing or deletion of Pink1 promoted excessive osteoclast differentiation and bone resorption in vitro, as respectively indicated by TRAP staining and resorption pits on dentin slices. PINK1 deficiency led to mitochondrial instabilities as indicated by confocal microscopy of mitochondrial ROS, mitochondrial oxygen consumption rate (OCR) analysis, and transmission electron microscopy (TEM). Consequently, a significant increase in Ca2+-nuclear factor of activated T cells 1 (NFATc1) signaling was also found. On the other hand, restoration of mitophagy and autophagy by spermidine (SPD) treatment and the resolution of oxidative stress by N-acetyl-l-cysteine (NAC) treatment protected PINK1 deficiency-induced excessive generation of osteoclasts. Taken together, our findings demonstrate that PINK1 is essential for maintaining mitochondrial homeostasis during osteoclast differentiation. Therefore, targeting PINK1 may provide a novel therapeutic strategy for severe periodontitis with fulminant osteolysis.
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Pérdida de Hueso Alveolar , Periodontitis , Animales , Ratones , Pérdida de Hueso Alveolar/complicaciones , Pérdida de Hueso Alveolar/tratamiento farmacológico , Ratones Endogámicos C57BL , Mitofagia/genética , Osteoclastos/metabolismo , Periodontitis/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The purpose of this study was to investigate the effects of different peri-implantitis treatment methods (Er,Cr:YSGG laser, diode laser, and electrocautery) on various titanium implant surfaces: machined; sandblasted, large-grit, and acid-etched; and femtosecond laser-treated surfaces. Grade 4 titanium (Ti) disks, with a diameter of 10 mm and a thickness of 1 mm, were fabricated and treated using the aforementioned techniques. Subsequently, each treated group of disks underwent different peri-implantitis treatment methods: Er,Cr:YSGG laser (Biolase, Inc., Foothill Ranch, CA, USA), diode laser (Biolase, Inc., Foothill Ranch, CA, USA), and electrocautery (Ellman, Hicksville, NY, USA). Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and wettability were used to characterize the chemical compositions and surfaces of the treated titanium surfaces. Significant changes in surface roughness were observed in both the electrocautery (Sa value of machined surface = 0.469, SLA surface = 1.569, femtosecond laser surface = 1.741, and p = 0.025) and Er,Cr:YSGG laser (Ra value of machined surface = 1.034, SLA surface = 1.380, femtosecond laser surface = 1.437, and p = 0.025) groups. On femtosecond laser-treated titanium implant surfaces, all three treatment methods significantly reduced the surface contact angle (control = 82.2°, diode laser = 74.3°, Er,Cr:YSGG laser = 73.8°, electrocautery = 76.2°, and p = 0.039). Overall, Er,Cr:YSGG laser and electrocautery treatments significantly altered the surface roughness of titanium implant surfaces. As a result of surface composition after different peri-implantitis treatment methods, relative to the diode laser and electrocautery, the Er,Cr:YSGG laser increased oxygen concentration. The most dramatic change was observed after Er:Cr;YSGG laser treatment, urging caution for clinical applications. Changes in surface composition and wettability were observed but were not statistically significant. Further research is needed to understand the biological implications of these peri-implantitis treatment methods.
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This study evaluated the effects of various mechanical debridement methods on the surface roughness (Ra) of dental implants, comparing femtosecond laser-treated surfaces with conventionally machined and sandblasted with large-grit sand and acid-etched (SLA) implant surfaces. The fabrication of grade 4 titanium (Ti) disks (10 mm in diameter and 1 mm thick) and the SLA process were carried out by a dental implant manufacturer (DENTIS; Daegu, Republic of Korea). Subsequently, disk surfaces were treated with various methods: machined, SLA, and femtosecond laser. Disks of each surface-treated group were post-treated with mechanical debridement methods: Ti curettes, ultrasonic scaler, and Ti brushes. Scanning electron microscopy, Ra, and wettability were evaluated. Statistical analysis was performed using the Kruskal-Wallis H test, with post-hoc analyses conducted using the Bonferroni correction (α = 0.05). In the control group, no significant difference in Ra was observed between the machined and SLA groups. However, femtosecond laser-treated surfaces exhibited higher Ra than SLA surfaces (p < 0.05). The application of Ti curette or brushing further accentuated the roughness of the femtosecond laser-treated surfaces, whereas scaling reduced the Ra in SLA surfaces. Femtosecond laser-treated implant surfaces, with their unique roughness and compositional attributes, are promising alternatives in dental implant surface treatments.
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Background and Objectives: The purpose of this study is to assess the long-term maintenance of each approach of sinus elevation, the crestal approach and lateral approach, by comparing the radiographic results of each technique. Materials and Methods: In total, 103 patients who had undergone an implant procedure with either the crestal approach or lateral approach method applied to their maxillary molar edentulous area were included. Using orthopantomographs, the radiographic changes were consistently evaluated over 3 years after the procedure (immediately after procedure and 1 year, 2 years and 3 years after implant placement) Results: The radiographic evaluation after 3 years of implantation with sinus elevation showed a significant amount of bone formation (8.07 mm for crestal approach and 12.00 mm for lateral approach method). The largest amount of grafted height loss occurred during the 1 year, but the resorption was minimal (0.98 mm for crestal approach and 0.95 mm for lateral approach method) over the entire 3 years. Conclusions: Although the lateral approach showed more bone growth, the amount of bone resorption was similar to that of the crestal approach. Both methods showed the highest amount of bone resorption in the first year, and the amount of change thereafter was insignificant. It is judged that both methods can be used according to the situation to help implant placement.
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Pérdida de Hueso Alveolar , Elevación del Piso del Seno Maxilar , Humanos , Estudios Longitudinales , Elevación del Piso del Seno Maxilar/métodos , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/cirugía , Osteogénesis , Pérdida de Hueso Alveolar/diagnóstico por imagen , Maxilar/diagnóstico por imagen , Maxilar/cirugíaRESUMEN
Background and Objectives: The purpose of this study is to observe the usefulness of autogenous tooth transplantation by examining the cumulative survival rate according to the period of auto-transplanted teeth as pre-implant treatment. Materials and Methods: This study was conducted on 111 patients who visited Kyungpook National University Dental Hospital and underwent autogenous tooth transplantation between November 2008 and January 2021 (about 13 years). The cumulative survival rate of autogenous tooth transplantation according to the causes of extraction of the recipient tooth (caries, periapical lesion, crack, crown fracture, periodontitis) and condition of opposing teeth (natural teeth vs. fixed prosthesis). The cumulative survival rate of autogenous tooth transplantation according to the age (under 30 vs. over 30) was also investigated and it was examined whether there were any differences in each factor. Results: The average follow-up period was 12 months, followed by a maximum of 162 months. The 24-month cumulative survival rate of all auto-transplanted teeth was 91.7%, 83.1% at 60 months and the 162-month cumulative survival rate was 30.1%. There were no statistical differences between the causes of extraction of the recipient's teeth, differences in the condition of the opposing teeth, and differences under and over the age of 30. Conclusions: The survival rate of autogenous tooth transplantation appears to be influenced by the conditions of the donor tooth rather than the conditions of the recipient tooth. Although autogenous tooth transplantation cannot completely replace implant treatment, it is meaningful in that it can slightly delay or at least earn the time until implant placement is possible.
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Fracturas de los Dientes , Diente , Humanos , Tasa de Supervivencia , Diente/trasplante , Trasplante Autólogo , Extracción Dental , Estudios de Seguimiento , Resultado del TratamientoRESUMEN
The present study aimed to confirm the usefulness of a multi-laser handpiece system currently under development. Implants were placed in the tibia of rabbits using a conventional separate laser-implant handpiece system (control group; SurgicPro+; NSK, Kanuma, Japan and Epic 10; Biolase, Irvine, CA, USA) and a multi-laser handpiece system (experimental group; BLP 10; Saeshin, Daegu, Korea). Implants were placed in left and right tibias of five rabbits using a conventional laser-implant handpiece system and a multi-laser handpiece system (N = 5 per group). Subsequently, micro-computed tomography (micro-CT; bone-to-implant contact evaluation), implant stability quotient (ISQ) measurement, and histological evaluations were performed to confirm the implant placement results. The independent t-test and the paired t-test were used to compare the ISQ values and the results of the two implant-laser handpiece groups (α = 0.05), respectively. No statistically significant difference in micro-CT, ISQ, and histological evaluations was observed between implant placement by the two systems (p > 0.05) except implant initial stability. The use of the multi-laser handpiece system is expected to produce the same results as a conventional separate laser-implant handpiece system with the higher implant initial stability. Additionally, it will potentially make the clinical environment more pleasant and will provide convenience for the clinicians.
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Periodontitis is an excessive inflammatory event in tooth-supporting tissues and can cause tooth loss. We used erythropoietin (EPO), which has been reported to play an important role in bone healing and modulation of angiogenesis, as a therapeutic agent in vivo and in vitro experimental models to analyze its effect on periodontitis. First, EPO was applied to in vitro MC3T3-E1 cells and human periodontal ligament fibroblast (hPDLF) cells to examine its function in altered cellular events and gene expression patterns. In vitro cultivation of MC3T3-E1 and hPDLF cells with 10 IU/ml EPO at 24 and 48 h showed an obvious increase in cell proliferation. Interestingly, EPO treatment altered the expression of osteogenesis-related molecules, including alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OC) in MC3T3-E1 cells but not in hPDLF cells. In particular, MC3T3-E1 cells showed increased expression of ALP, BMP-2, and OC on day 5, while hPDLF cells showed increased expression of BMP-2, and OC on day 14. Based on the in vitro examination, we evaluated the effect of EPO on bone formation using an experimentally-induced animal periodontitis model. After the induction of periodontitis in the maxillary left second M, 10 IU/ml of EPO was locally applied to the extraction tooth sockets. Histomorphological examination using Masson's trichrome (MTC) staining showed facilitated bone formation in the EPO-treated groups after 14 days. Similarly, stronger positive reactions against vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), runt-related transcription factor 2 (RUNX2), and osteocalcin (OC) were detected in the EPO-treated group compared to the control. Meanwhile, myeloperoxidase, an inflammatory marker, was decreased in the EPO-treated group on days 1 and 5. Overall, EPO facilitates bone healing and regeneration through altered signaling regulation and modulation of inflammation in the osteoblast cell lineage and to a lesser extent in hPDLF cells.
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This study aimed to examine the differences in healing patterns using two types of diode laser devices (laser A and laser B) and a steel scalpel for periodontal surgery through histological and immunohistochemical methods. Twenty 12-week-old male rats were assigned to three groups (3, 7, and 14 days). Square-shaped erosion wounds (2 × 2 mm2 diameter) were created on the hard palate of each rat. Two wounds were created using Laser A and a steel scalpel (Bard-Parker No. 15) on the right palate and using Laser B and a steel scalpel on the left side. Rats were sacrificed after 3, 7, and 14 days. Tissues were collected with a margin of 1 mm from the border of the erosional wound of the maxillary hard palate. Histological and immunohistochemical analyses were performed on the tissue samples after 3, 7, and 14 days. The tissue healing pattern and expression of inducible nitric oxide synthase (iNOS) and cluster of differentiation (CD) were observed under a light microscope. Statistical analysis was conducted using the Kruskal−Wallis H test for comparison among the groups (α = 0.05). In comparison to the wounds made with the scalpel, wounds treated with lasers A and B showed delayed healing patterns. There was no significant difference between the two laser treatment groups (p > 0.05). The expression of iNOS and CD68 was not significantly different among the three groups after 3 and 7 days (p > 0.05). On day 14, the groups treated with the dental diode lasers showed higher expression than the group treated with the steel scalpel, but no significant difference was observed (p > 0.05). Laser-induced wounds tended to heal slower than surgical wounds performed using a steel scalpel, but histological and immunohistochemical results showed no significant difference between the dental diode laser and scalpel groups.
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The differentiation and activity of bone-resorbing osteoclasts are tightly regulated to maintain the homeostasis of healthy bones. In this study, the role of protein tyrosine phosphatase 1B (PTP1B) during osteoclastogenesis was studied in myeloid-specific Ptpn1-deficient (conditional knockout [cKO]) mice. The mRNA and protein expression of PTP1B increased during the formation of mature osteoclasts from mouse bone macrophages on stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). The Ptpn1 cKO mice exhibited increased femoral trabecular bone volume with a decreased number and activity of osteoclasts compared with control mice. The in vitro culture of osteoclast precursors corroborated the inhibition of osteoclastogenesis in cKO cells compared with control, with concomitantly decreased RANKL-dependent proliferation, lower osteoclast marker gene expression, reduced nuclear expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), diminished intracellular Ca2+ oscillations, and increased phosphorylation of proto-oncogene tyrosine-protein kinase Src on inhibitory tyrosine residue. In a ligature-induced periodontitis model, Ptpn1 cKO mice exhibited attenuated osteoclastogenesis and alveolar bone loss following the induction of inflammation. The Ptpn1-deficient mice were similarly protected from ovariectomy-induced bone loss compared with control mice. These results provide a novel regulatory role of PTP1B in osteoclastogenesis and suggest a potential as a therapeutic target for bone-lytic diseases. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Resorción Ósea , Osteogénesis , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Animales , Resorción Ósea/metabolismo , Diferenciación Celular , Femenino , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Ovariectomía , Monoéster Fosfórico Hidrolasas/metabolismo , Ligando RANK/metabolismo , Tirosina/metabolismoRESUMEN
PURPOSE: To investigate factors affecting the antagonistic and adjacent teeth in patients after implant restoration and prosthetic rehabilitation. METHODS: In total, 160 patients who visited Kyungpook National University Dental Hospital for implant surgery, prosthesis placement, and supportive periodontal therapy (SPT) were included in this study. The average follow-up period was 88.06 months, and the maximum was 175 months. Patients' history of smoking, diabetes, hypertension, and osteoporosis was investigated, and panoramic radiographs were taken after surgery and prosthetic treatment. During the follow-up period, extraction and prosthetic/endodontic treatments of the antagonistic and adjacent teeth were analyzed. The statistical analyses were performed using descriptive statistics, the chi-square test, the Fisher exact test, and multiple logistic regression analyses. RESULTS: Treatment was performed on 29.4% of the studied antagonistic teeth with extraction performed in 20.0% and prosthetic treatment in 10.0%. Furthermore, 19.4% of the studied adjacent teeth underwent treatment, of which extraction was performed in 12.5% and prosthetic treatment in 7.5%. The treatment rate for adjacent teeth was 25.3% in smokers, which was higher than that of non-smokers (12.3%) (P=0.039). Patients who were non-adherent to SPT showed a significantly higher rate (19.6%) of antagonistic prosthetic treatment than did those who were adherent (5.5%) (P=0.006). CONCLUSIONS: Implant restoration can affect the adjacent and antagonistic teeth. Smoking, osteoporosis history, and absence of SPT may be risk factors for the treatment of the adjacent and antagonistic teeth.
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Periodontitis is caused by an oral microbial dysbiosis-mediated imbalance of the local immune microenvironment, which is promoted by insulin resistance and obesity. The prevalence and severity of periodontitis is higher in patients with type 2 diabetes than in healthy individuals, possibly because of differences in immune responses. The level of glycemic control also affects the saliva profile, which may further promote periodontal disease in diabetes patients. Therefore, we compared the salivary exosomal miRNA profiles of patients with type 2 diabetes with those of healthy individuals, and we found that exosomal miR-25-3p in saliva is significantly enriched (by approximately 2-fold, p < 0.01) in obese patients with type 2 diabetes. We also identified CD69 mRNA as a miR-25-3p target that regulates both activation of γδ T cells and the inflammatory response. Knockdown of CD69 increased (by approximately 2-fold) interleukin-17A production of γδ T cells in vitro. To evaluate the role of exosomal miRNA on progression of periodontitis, we analyzed regional immune cells in both periodontal tissues and lymph nodes from mice with periodontitis. We found that diet-induced obesity increased the population of infiltrating pro-inflammatory immune cells in the gingiva and regional lymph nodes of these mice. Treatment with miR-25-3p inhibitors prevented the local in vivo inflammatory response in mice with periodontitis and diet-induced obesity. Finally, we showed that suppression of interleukin 17-mediated local inflammation by a miR-25-3p inhibitor alleviated (by approximately 34%) ligature-induced periodontal alveolar bone loss in mice. Taken together, these data suggest that exosomal miR-25-3p in saliva contributes to development and progression of diabetes-associated periodontitis. Discovery of additional miR-25-3p targets may provide critical insights into developing drugs to treat periodontitis by regulating γδ T cell-mediated local inflammation.
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Diabetes Mellitus Tipo 2/inmunología , Exosomas/inmunología , Resistencia a la Insulina/inmunología , MicroARNs/inmunología , Periodontitis/inmunología , Saliva/inmunología , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Periodontitis/etiologíaRESUMEN
Many growth factors have been paired with synthetic bone grafts to accelerate the healing process in vivo. Collagen has been particularly examined as a mediator of the enhancement of bone regeneration. This study investigated the new bone formation potential of micro-macroporous biphasic calcium phosphate (m-BCP), high porosity biphasic calcium phosphate (p-BCP), and collagen-coated p-BCP (cp-BCP) using a rabbit calvarial defect model. At 2 or 8 weeks after surgery, bone tissue was collected. The three-dimensional analysis of new bone formation using synchrotron radiation micro-computed tomography and histological study were conducted. The new bone formation values observed at 2 and 8 weeks in the negative control, m-BCP, p-BCP, and cp-BCP groups were 11.21 ± 1.36 mm3, 21.75 ± 1.18 mm3, 24.59 ± 1.26 mm3, and 29.54 ± 2.72 mm3, respectively, and 18.34 ± 3.99 mm3, 32.27 ± 3.78 mm3, 43.12 ± 1.61 mm3, and 58.20 ± 3.84 mm3, respectively. New bone formation was greatest in the cp-BCP group, while the amount of new bone at 8 weeks was higher than at 2 weeks in each group. The use of cp-BCP to enhance new bone formation during the healing period could improve bone regeneration.