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1.
ObjectivesTemporomandibular joint osteoarthritis (TMJ-OA) causes degenerative changes in TMJ tissues. The inter-tissue crosstalk that exacerbates illness and organic changes in bone secondary to TMJ-OA potentially affects the muscles; therefore, patients with a muscular disease might also suffer from bone disease. However, knowledge gaps exist concerning muscle pathology at the onset of TMJ-OA. In this study, we documented the pathogeneses of the bone and muscle at the onset of TMJ-OA using a mouse model.MethodsWe performed a partial resection of the TMJ disk to establish a mouse model of TMJ-OA. After the onset of TMJ-OA, we performed various measurements at 8, 12, and 16 weeks post-surgery in the defined groups.ResultsThe volume of the mandibular head in the TMJ-OA group was significantly greater than that in the control group. The temporal muscles in the TMJ-OA group were significantly deformed compared with those in the control group; however, between-group comparisons did not reveal significant differences in the mandibular head or temporal muscles after surgery. Therefore, we hypothesized that the degree of mandibular head hypertrophy would alter the temporal muscles. A subsequent analysis of the correlation between the bone and muscle confirmed that the deformity of the temporal muscle increased with increasing hypertrophy of the mandibular head. Temporal and masseter muscle contact was observed in 25% of surgical groups.ConclusionsThis study demonstrates that TMJ-OA progressed when organic changes occurred in bones and muscles, supporting the symbiotic relationship between bones and muscles.  相似文献   

2.
《Saudi Dental Journal》2022,34(3):237-242
BackgroundPrevious studies have demonstrated that SARS-CoV-2 is mainly transmitted by inhalation of aerosols and can remain viable in the air for hours. Viruses can spread in dental settings and put professionals and patients at high risk of infection due to proximity and aerosol-generating procedures, and poor air ventilation.ObjectivesThe aim of this study was to investigate the effects of a 1% hydrogen peroxide (H2O2) mouth rinse on reducing the intraoral SARS-CoV-2 load.MethodsPortable air cleaners with HEPA filters exposed for 3 months were analysed to test for virus presence in a waiting room (where patients wore a face mask but did not undergo mouth rinsing) and three treatment rooms (where patients wore no mask but carried out mouth rinsing). As CO2 is co-exhaled with aerosols containing SARS-CoV-2 by COVID-19 infected people, we also measured CO2 as a proxy of infection risk indoors. Specific primer and probe RT-PCR were applied to detect viral genomes of the SARS-CoV-2 virus in the filters. Specifically, we amplified the nucleocapsid gene (Nuclv) of SARS-CoV-2.ResultsCO2 levels ranged from 860 to 907 ppm, thus indicating low ventilation and the risk of COVID-19 transmission. However, we only found viral load in filters from the waiting room and not from the treatment rooms. The results revealed the efficiency of 1-minute mouth rinsing with 1% H2O2 since patients rinsed their mouths immediately after removing their mask in the treatment rooms.ConclusionsOur findings suggest that dental clinics would be safer and more COVID-19 free by implementing mouth rinsing 1 min with 1% H2O2 immediately after the patients arrive at the clinic.  相似文献   

3.
BackgroundGiven equivocal findings from existing nationally representative studies, the authors sought to determine associations between vitamin D levels and caries experience in US children using updated National Health and Nutrition Examination Survey data.MethodsThe authors used data from 2011-2016 National Health and Nutrition Examination Survey. Vitamin D status was assessed on the basis of the sufficiency thresholds of 50 and 75 nmol/L for serum 25-hydroxyvitamin D (25[OH]D) recommended by the Institute of Medicine (now National Academy of Medicine) and Endocrine Society, respectively. Caries experience was defined as the total number of decayed or filled tooth surfaces (dfs) and decayed, missing, or filled tooth surfaces (DMFS) and a binary measure of any dfs and DMFS. Associations between 25(OH)D and any or total dfs and DMFS were examined in children aged 2 through 5, 6 through 8, 9 through 11, and 12 through 18 years, using multivariable logistic and linear regression models after adjustment for covariates.ResultsChildren aged 2 through 5 years with 25(OH)D above 75 nmol/L experienced fewer total dfs (β = –1.94; 95% CI, –3.60 to –0.28) than those with 25(OH)D below 75 nmol/L. Children 6 through 8 years with 25(OH)D above 75 nmol/L had lower presence of any dfs (odds ratio, 0.59; 95% CI, 0.36 to 0.95) than those with 25(OH)D below 75 nmol/L, and those with 25(OH)D above 50 nmol/L had lower presence of any DMFS (odds ratio, 0.38; 95% CI, 0.19 to 0.79) than those with 25(OH)D below 50 nmol/L. There were no associations of 25(OH)D status with either any or total DMFS in children 12 through 18 yearsConclusionsThere were no consistent associations of 25(OH)D status with caries experience across age groups.Practical ImplicationsVitamin D status was not associated consistently with reduced caries experience.  相似文献   

4.
ObjectivesPeriodontal ligament-derived stem cells (PDLSCs) are regarded as a viable option for periodontal regeneration using cell sheet technology. The objective of the present in vitro study was to characterize human PDLSCs based on their phenotypic and biological properties and to evaluate the ascorbic acid (AA or vitamin C)-induced cell sheet by analyzing the molecular markers.MethodsPDLSCs were established from premolars, and their morphology, viability, proliferation, phenotypic marker expression, and ability to differentiate into osteocytes and adipocytes were analyzed. PDLSCs were then induced to form cell sheets using 100 μM AA, and gene expression was examined by real-time polymerase chain reaction.ResultsPDLSCs showed fibroblastic morphology with >95% viability. The cells were highly proliferative and positive for surface antigens CD29, CD73, and CD90 but negative for CD34 and CD45. They were capable of differentiating into osteocytes and adipocytes. Induction with 100 μM AA transformed PDLSCs into two-to three-layered cell sheets. There was no significant upregulation in ALP and RUNX2 expression in the AA-induced cell sheet. However, the expression levels of late osteoblast differentiation marker (bone gamma-carboxy glutamate protein); cementogenic markers (cementum attachment protein and CP23), and genes encoding extracellular matrix (ECM) proteins [collagen type 1 alpha 1 and integrin beta 1) were higher in AA-induced cell sheets by PDLSCs.ConclusionsThe stimulating effect of AA on cell sheet formation by PDLSCs was confirmed by the expression of typical markers involved in osteogenesis/cementogenesis and ECM secretion, which makes this procedure a prospective option for periodontal tissue regeneration applications.  相似文献   

5.
ObjectivesOsteoclasts can sense the surface topography of materials. However, it is difficult to identify the structural factors that affect osteoclast formation and its function. Furthermore, we hypothesized that the type of osteoclast precursor cells also affects osteoclastogenesis in the materials. In this study, we investigated the effects of defined micro/nanoscale patterns on osteoclastogenesis from bone marrow cells (BMCs).MethodsVarious cyclo-olefin polymer (COP) patterns were prepared using nanoimprinting. The effects of shape, size, and height of the patterns, and the wettability of the patterned surfaces on osteoclastogenesis from BMCs were evaluated in vitro.ResultsOsteoclast formation was promoted on pillars (diameter, 1 μm or 500 nm; height, 500 nm). Notably, osteoclastogenesis from BMCs was better promoted on hydrophobic pillars than on hydrophilic pillars. In contrast, decreased osteoclast formation was observed on the nanopillars (diameter, 100 nm; height, 200 nm).ConclusionsWe demonstrated the promotion of osteoclast formation from BMCs on hydrophobic pillars with diameters of 1 μm and 500 nm. Some cellular behaviors in the patterns were dependent on the type of osteoclast precursor cells. The designed patterns are useful for designing the surface of dental implants or bone replacement materials with a controllable balance between osteoblast and osteoclast activities.  相似文献   

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ObjectivesThe self-regeneration of exocrine tissues, including salivary glands, is limited and their regeneration mechanism has not yet been fully elucidated. Here we identify the role of adipose-derived mesenchymal stem cells (AMSCs) in salivary gland regeneration.MethodsAMSCs expressing mesenchymal stem cell markers were applied to a submandibular gland injury model and the mechanism of salivary gland repair and regeneration was analyzed.ResultsTransplanted green fluorescent protein (GFP)-labeled AMSCs grew tightly together and promoted ductal regeneration in the regenerative nodule, with slight infiltration of nonspecific immune cells. A comprehensive gene analysis through RNA-sequencing revealed increased expression of bone morphogenetic protein (BMP), transforming growth factor (TGF), and Wnt in AMSC-transplanted regenerative nodules. The factors released from AMSCs scavenge hydrogen peroxidase-induced reactive oxygen species (ROS) through Wnt promoter activity in vitro. Furthermore, AMSC-conditioned medium recovered the growth of the hydrogen peroxidase-damaged primordium of the submandibular gland culture ex vivo.ConclusionsThese results suggest that AMSC-released factors scavenge ROS and maintain salivary gland repair and regeneration via paracrine effects. Thus, AMSCs could be a practical and applicable tool for use in salivary gland regeneration.  相似文献   

8.
ObjectivesCalcium phosphate/SLS/P123 composite bioactive gels were prepared to achieve dentine tubule occlusion.MethodsGels containing calcium phosphate particles were prepared in a water-in-oil microemulsion system with a mixture of triblock copolymer pluronic (P123) as a co-surfactant and sodium lauryl sulfate (SLS) as a surfactant in cyclohexane. Subsequently, calcium chloride dihydrate and sodium hydrogen phosphate aqueous solutions were added in a water phase. Finally, slow evaporation of the oil phase at room temperature was performed to produce a hybrid gel. The obtained gels were investigated for their toxicity by the sulforhodamine B (SRB) assay and applied on human dentine specimens to examine their ability to occlude dentine tubules.ResultsThe size and morphology of the calcium phosphate particles embedded in the gel depended on the concentration of P123 and SLS, which were used as a template for mineral precipitation. The prepared calcium phosphate particles (200–500 nm in diameter) with the maximum polymer and surfactant content exhibited spherical shapes. Further, on reducing their content twice and tenfold yields micro-particles with flower-like shapes. These bioactive gels were able to occlude into dentine tubules after 3 days of application with a plugging rate of 79.22% when using the smallest particles. In addition, calcium phosphate nanorods were transformed into dentine tubules with a maximum depth of 6 μm on increasing the amount of gel.ConclusionsThe bioactive gels were effectively used as bioactive fillers to occlude exposed human dentine tubules.  相似文献   

9.
ObjectivesThe aim of this behavioral study was to investigate the duration of a conditioned stimulus (CS-duration) necessary for rats to recognize the components of a binary taste mixture in a conditioned taste aversion (CTA) paradigm as well as the relationship between CS-duration and their spontaneous recovery.MethodsThe experimental rats were categorized under conditioned and control groups and further divided into three groups according to the CS-duration: 10, 30, and 60 s. As the test stimuli, a mixture of 100 mM sucrose (S) + 30 μM quinine hydrochloride (Q) and its components were used.ResultsOn day 1 of the CTA test, the number of licks (NL) for S + Q and S in all conditioned groups was significantly lower than that of the control group presented with CS for 60 s (CON-60), which was the representative control group determined by the initial CTA test. For Q, there was no significant difference between NL of the CTA group presented with CS for 10 s and that of CON-60; however, NL in the other two CTA groups, i.e., CTA-30 and CTA-60, was significantly lower than that of CON-60. When the rats were presented with a shorter CS-duration, they showed spontaneous recovery earlier depending on the CS-duration.ConclusionsThese results suggest that rats can recognize a binary taste mixture and its components using a CS-duration of more than 30 s and that spontaneous recovery from CTA learning depends on the CS- duration.  相似文献   

10.
ObjectivesRecombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in arginine-glycine-aspartic acid sequences with good processability whose use for regenerative medicine applications is under investigation. The biocompatibility and osteogenic ability of RCP granules combined with β-tricalcium phosphate (TCP) submicron particles (β-TCP/RCP) were recently demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects created in beagles to investigate its regenerative effects.MethodsAn RCP solution was lyophilized, granulated, and thermally cross-linked into particles approximately 1 mm in diameter. β-TCP dispersion (1 wt%; 500 μL) was added to 100 mg of RCP granules to form β-TCP/RCP. A three-walled intrabony defect (5 mm × 3 mm × 4 mm) was created on the mesial side of the mandibular first molar and filled with β-TCP/RCP.ResultsA micro-computed tomography image analysis performed at 8 weeks postoperative showed a significantly greater amount of new bone after β-TCP/RCP grafting (2.2-fold, P < 0.05) than after no grafting. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including tartaric acid-resistant acid phosphatase– and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements performed at 8 weeks postoperative revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control condition and significantly suppressed gingival recession and epithelial downgrowth (P < 0.05).Conclusionsβ-TCP/RCP implantation promoted bone-like and periodontal ligament–like tissue formation, suggesting its efficacy as a periodontal tissue regenerative material.  相似文献   

11.
《Dental materials》2022,38(2):421-430
ObjectivesTo determine the long-term effect on the stability of dentin-resin interfaces after the addition of polylactide (PLA) capsules containing proanthocyanidin (PAC) to adhesive resin.MethodsSub-micron (SM) and micron (M) size capsules containing PACs were produced using a combination of emulsification and solvent evaporation techniques and characterized. Human dentin surfaces (n = 8) were etched (35% glycolic acid) and primed (15% enriched Vitis vinifera extract solution - VVe), followed by the application of an experimental adhesive containing 0 (control), 1.5 wt% of SM or M PAC-filled PLA capsules light cured for 40 s. A crown was built using commercial composite. After 24 h-immersion (37 °C) in simulated body fluid, specimens were serially sectioned into resin-dentin beams. Microtensile bond strength (TBS), micro-permeability and fracture pattern were assessed immediately and after 1 and 2 years. Data were statistically analyzed using two-way ANOVA and post-hoc test (α = 0.05).ResultsPolydisperse capsules were manufactured with average diameter of 0.36 µm and 1.08 µm for SM and M, respectively. The addition of capsules did not affect TBS (p = 0.889). After 2 years, TBS significantly decreased in SM (p = 0.006), whereas M showed similar initial values (p = 0.291). Overall, less micro-permeability was found in M than the control and SM group (p < 0.001). After 2 years, fractured surfaces from capsule-containing groups failed within the adhesive layer while control fractured at the bottom of the hybrid layer.SignificanceThe addition of PAC-filled PLA microcapsules in a dental adhesive did not affect the bond strength while increased and sustained the protection against micro-permeability in the interface, likely due to release of PACs.  相似文献   

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ObjectivesThe aim of the present study was to demonstrate the effective dose of emetine for inducing nausea and/or emesis, and the effects of emetine on the excitability of central neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS).MethodsRats were used as experimental animals. We measured the conditioned taste aversion (CTA) induced by the intraperitoneal administration of emetine solution (0.03, 0.1, 0.3, 0.5, and 1.0 mM in saline) and that of only saline. We also performed immunohistochemical analyses of c-Fos expression in the area postrema and the NTS, to examine changes in the excitability of brainstem neurons that may be responsible for emetine-induced nausea and/or emesis.ResultsThe emetine-induced CTA occurred in a dose-dependent manner. The half maximal inhibitory concentration (IC50) of emetine on the saccharin preference was calculated to be 0.348 mM using the Hill equation. In the animals injected with emetine (0.5 and 1.0 mM), many c-Fos-like immunoreactive (Fos-ir) cells were observed in the area postrema and the NTS, while few Fos-ir cells were identified in the animals injected with saline. The average number of Fos-ir cells in the area postrema and the NTS was significantly larger in animals injected with emetine than in animals injected with saline.ConclusionsThe present study demonstrated a dose-responsive manner of emetine effects and emetine-induced upregulation of neuronal excitability in the area postrema and the NTS that form a part of the induction mechanisms of emetine-induced nausea and/or emesis.  相似文献   

14.
ObjectivesThis study aimed to evaluate the repair of critical-sized bone defects grafted with autogenous bone and mercerized bacterial cellulose membranes (BCm) salified with alendronate (ALN).MethodsForty-eight male Wistar rats underwent surgery to create a 5 mm-diameter bone defect in the calvarium. The removed bone was particularized, regrafted into the defect, and covered by a BCm according to the group: control group (CG), simply mercerized BCm; group 1 (G1), negatively charged BCm (BCm-CM-) salified with ALN; and group 2 (G2), positively charged BCm (BCm-DEAE+) salified with ALN. Serum samples were collected preoperatively and before euthanasia to analyze osteoprotegerin (OPG), parathyroid hormone (PTH), sclerostin (SOST), and fibroblast growth factor 23 (FGF23) levels. The animals were euthanized after 15 or 60 d. Calvaria were analyzed using quantitative microtomography (μCT).ResultsThere was an increased level of PTH in the CG compared to the G2 group, at day 60 (p = 0.019). When analyzing the same group over time, G1 presented an increased FGF23 level on days 15 and 60 (p < 0.05). CG presented an increase in PTH (p = 0.037) at day 60. The μCT analysis detected increased trabecular separation on day 15 in G2 compared to G1 (p = 0.040).ConclusionsSalification of ionized BCm with ALN had no direct effect on bone repair; however, BCm-CM- increased the levels of FGF23 over time. BCm-DEAE+ decreased PTH levels compared to mercerized BCm. BCm-CM-salified with ALN-induced superior bone quality, with respect to trabecular separation, compared to BCm-DEAE+.  相似文献   

15.
ObjectivesMyocardial ischemia-reperfusion injury is a phenomenon that promotes myocardial damage when the blood supply returns to the tissue after a period of ischemia. Anesthetic postconditioning involves myocardial protection against myocardial I/R injury. The effects of atorvastatin (ATV) on sevoflurane postconditioning against myocardial ischemia-reperfusion injury have not been thoroughly studied. The present study aimed to investigate if ATV interacts synergistically with sevoflurane postconditioning against myocardial infarction in rabbit hearts in vivo.MethodsTwenty-eight male rabbits underwent 30 min of left anterior descending coronary artery occlusion that was followed by reperfusion for 180 min under ketamine/xylazine (K/X) anesthesia. Rabbits were randomly assigned to four groups that included Group K/X (under K/X anesthesia only), Group POST (sevoflurane exposure at initial reperfusion), Group ATV (ATV 5 mg/kg/day administered before ischemia), and Group ATV + POST (POST intervention with atorvastatin administered once daily for 3 days). At the end of reperfusion, the myocardial infarct size and the area at risk were both measured.ResultsThe mean infarct sizes in the POST, ATV, and ATV + POST groups were significantly smaller compared to those in the K/X group. Furthermore, the mean infarct size in Group ATV + POST was significantly smaller than was that in Group POST and significantly smaller compared to that in Group ATV.ConclusionThe combination of sevoflurane postconditioning and pre-administration of ATV further reduced the myocardial infarction size compared to that observed with sevoflurane postconditioning alone or ATV alone. Our data suggest that sevoflurane postconditioning and ATV may function additively to enhance cardioprotection.  相似文献   

16.
《Saudi Dental Journal》2022,34(7):565-571
PurposeThis study aimed to evaluate the neuroprotective ability of the conditioned medium of stem cells from human exfoliated deciduous teeth (CM-SHED) to prevent glutamate-induced apoptosis of neural progenitors.Materials and methodsNeural progenitors were isolated from two-day-old rat brains, and the conditioned medium was obtained from a mesenchymal stem cell SHED. Four groups were examined: neural progenitor cells cultured in neurobasal medium with (N + ) and without (N-) glutamate and glycine, and neural progenitor cells cultured in CM-SHED with (K + ) and without (K-) glutamate and glycine.ResultsThe expression of GABA A1 receptor (GABAAR1) messenger RNA (mRNA) in neural progenitor measured by real-time quantitative PCR. GABA contents were measured by enzyme-linked immunosorbent assay, whereas the apoptosis markers caspase-3 and 7-aminoactinomycin D were analysed with a Muse® cell analyzer. The viability of neural progenitor cells in the K + group (78.05 %) was higher than the control group N- (73.22 %) and lower in the N + group (68.90 %) than in the control group. The K + group showed the highest GABA content, which significantly differed from that in the other groups, whereas the lowest content was observed in the N + group. The expression level of GABAAR1 mRNA in the K + group was the highest compared to that in the other groups. CM-SHED potently protected the neural progenitors from apoptosis.ConclusionsCM-SHED may effectively prevent glutamate-induced apoptosis of neural progenitors.  相似文献   

17.
BackgroundPorphyromonas gingivalis is a causative agent of chronic periodontitis. Standard strains of P. gingivalis, such as W83 and ATCC 33277, proliferate in minimal medium when protein is added as the energy source and hemin and menadione are added as growth factors. Nevertheless, minimal medium containing bovine serum albumin sometimes fails to support growth.HighlightsThe proliferation of two W83 strains and seven ATCC 33277 strains in various minimal media was investigated. Previously, we determined that calcium chloride (CaCl2) was a growth factor for W83NM, a W83 strain. In this study, we found that vitamin B12 enhanced the proliferation of W83NM in a minimal medium with cultures from the fourth passage but not from the first to the third passage. Therefore, using fourth-passage cultures, we assessed the proliferation of two W83 and seven ATCC 33277 strains in minimal media and the effects of CaCl2 and vitamin B12. Surprisingly, the nine P. gingivalis strains all differed with respect to their proliferation in minimal media, and protein products used as energy sources showed product-to-product and lot-to-lot heterogeneity. Even though strains or protein products were different, we found CaCl2-dependent growth in nine strains and vitamin B12-dependent growth in seven strains.ConclusionThese results suggest that calcium ions and vitamin B12 are novel growth factors for P. gingivalis.  相似文献   

18.
ObjectivesRhabdomyosarcoma (RMS) involving the parameningeal-nonparameningeal region (PNP) is relatively rare in pediatric patients (PPs). The current study aimed to report the outcomes of RMS-PNP-PPs who received surgical resection combined with concurrent flap reconstruction.MethodsA retrospective study was conducted concerning RMS-PNP-PPs who received combined skull-maxillofacial resection with flap reconstruction during the period from 2012 to 2016. Predictive factors for recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS) were preliminarily identified by Kaplan–Meier analysis.ResultsA total of 16 RMS-PNP-PPs were finally enrolled; recurrence, metastasis and death were found in 7, 7 and 5 patients, respectively. Following surgical ablation involving the skull base and maxillofacial region, reconstruction was performed with a local flap in 9 patients, a latissimus dorsi flap in 3 patients, and an anterolateral thigh flap in 4 patients. Through univariate analysis, we demonstrated that the primary site + surgical margins, postoperative RT/CT + Ki-67/Bcl-2 IHC, and surgical margins + Ki-67/Bcl-2 IHC could be used as the preliminarily prognostic factors for RFS, MFS and OS, respectively.ConclusionsRMS-PNP-PPs showed poor prognosis even when surgical resection combined with flap reconstructions was performed. Achieving a clear surgical margin and good conduction of postoperative RT/CT should be taken into consideration to acquiring a better surgical outcome.  相似文献   

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ObjectivesTo investigate plasma osteopontin (OPN) and osteocalcin (OCN) levels in dental patients with carotid artery calcification (CAC) and determine the correlations between these proteins and renal function and tooth loss.MethodsThe health parameters and number of teeth of 99 participants were recorded. Panoramic radiographs were taken for CAC evaluation, and OPN and OCN levels were measured.ResultsNone of the participants had overt kidney disease, and 14 (14.14%) had CAC. The age, sex, and health profiles of patients with CAC were not different from those without CAC. The OPN and OCN levels in participants with CAC were higher than in those without (p = 0.026 and p = 0.025, respectively). The OPN levels were correlated with the estimated glomerular filtration rate (eGFR) (p = 0.021) and tooth loss (p = 0.027). The OCN levels were correlated with the eGFR (p = 0.002), tooth loss (p = 0.023), blood urea nitrogen (p = 0.040), and creatinine levels (p = 0.031). The median tooth loss in individuals with an eGFR <60 mL/min/1.73 m2 was higher than that of individuals with an eGFR ≥60 mL/min/1.73 m2 (p = 0.033). In individuals with CAC, tooth loss correlated more strongly with the eGFR, and the correlation between OPN and OCN levels was more apparent.ConclusionDental patients with CAC and increased tooth loss have a greater tendency for decreased renal function, which may be associated with OPN and OCN; thus, these patients should be referred for investigation.  相似文献   

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