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PURPOSE: The purpose of this study was to assess whether kinematic alignment (KA) outperforms mechanical alignment (MA) in restoring patellar tracking to native patterns by using a clustering algorithm. METHODS: Twenty cadavers (40 knees) were evaluated. For each cadaver, one knee was randomly assigned to KA and the other to MA. KA total knee arthroplasty (TKA) procedures were performed using a caliper-verified technique, while MA TKA procedures utilized a measured resection technique. Subsequently, all specimens were mounted on a customized knee-testing system, and patellar tracking was measured using a motion analysis system. All patellar tracking data were clustered using the density-based spatial clustering of applications with noise algorithm. Differences in patellar tracking patterns and the restoration of native patellar tracking were compared between the two alignment strategies. RESULTS: Patellar tracking patterns following KA were considerably different from MA. Pre- and post-TKA patellar tracking patterns following MA were grouped into separate clusters, whereas a substantial proportion of patellar tracking patterns following KA were grouped into the pre-TKA dominant cluster. Compared to MA, a greater proportion of patellar tracking patterns following KA showed similar patterns to native knees (p < 0.05) and more patellar tracking patterns following KA paired with preoperative patterns (p < 0.01). CONCLUSION: KA restored native patellar tracking patterns more closely compared to MA. LEVEL OF EVIDENCE: Level I, therapeutic study.
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Background and Objectives: Recent advancements in three-dimensional printing technology have enhanced the biologic fixation of cementless total knee arthroplasty (TKA), therefore increasing the utilization of newer-generation cementless implants. However, the lack of sealing and tamponade effect of cement on the resected bone surface after cementless TKA raises concerns regarding the potential for greater blood loss compared to cemented TKA. The aim of this study was to (1) compare blood loss and transfusion rates between cementless and cemented TKAs and (2) identify the risk factor for higher blood loss in patients who underwent 1-week-interval staggered bilateral (SB) TKA. Materials and Methods: This retrospective, propensity-matched study included 54 cementless and 53 cemented SB TKAs performed by a single surgeon from 2019 to 2023 with a single implant that has similar design features in both cementless and cemented implants. All patients underwent 1-week-interval SB TKA and received the same patient blood management (PBM) and rehabilitation protocol. The estimated total blood loss (TBL), transfusion rate, and total hemoglobin drop were assessed. Patients were categorized according to TBL into average TBL and higher TBL groups. Univariate and multiple logistic regression analyses were performed to identify risk factors for higher blood loss. Results: There was no difference in TBL between cementless and cemented TKA groups (1233 ± 299 and 1282 ± 309 mL, respectively; p > 0.05). In addition, no between-group differences in the transfusion rate and mean total hemoglobin drop were observed. The logistic regression analyses revealed that whether TKA was cementless or cemented was not associated with higher blood loss; rather, the only identified risk factor was the pre-TKA patient blood volume (odd ratio 1.001, 95% confidence interval 1.000-1002, p = 0.026). Conclusions: Contemporary cementless fixation does not increase blood loss or transfusion rates compared to cemented fixation in patients undergoing 1-week-interval staggered bilateral TKA.
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Artroplastia do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Hemorragia , HemoglobinasRESUMO
Background and Objectives: Guided-motion bicruciate-stabilized (BCS) total knee arthroplasty (TKA) includes a dual cam-post mechanism with an asymmetric bearing geometry that promotes normal knee kinematics and enhances anterior-posterior stability. However, it is unclear whether the improved biomechanics after guided-motion BCS TKA reproduce soft tissue strain similar to the strain generated by native knees. The purpose of this cadaveric study was to compare medial collateral ligament (MCL) strain between native and guided-motion BCS TKA knees using a video extensometer. Materials and Methods: Eight cadaver knees were mounted onto a customized knee squatting simulator to measure MCL strain during flexion in both native and guided-motion BCS TKA knees (Journey II-BCS; Smith & Nephew, Memphis, TN, USA). MCL strain was measured using a video extensometer (Mercury® RT RealTime tracking system, Sobriety s.r.o, Kurim, Czech Republic). MCL strain level and strain distribution during knee flexion were compared between the native and guided-motion BCS TKA conditions. Results: The mean and peak MCL strain were similar between native and guided-motion BCS TKA knees at all flexion angles (p > 0.1). MCL strain distribution was similar between native and BCS TKA knees at 8 of 9 regions of interest (ROIs), while higher MCL strain was observed after BCS TKA than in the native knee at 1 ROI in the mid portion of the MCL at early flexion angles (p < 0.05 at ≤30° of flexion). Conclusions: Guided-motion BCS TKA restored the amount and distribution of MCL strain to the values observed on native knees.
Assuntos
Artroplastia do Joelho , Ligamentos Colaterais , Humanos , Rotação , Articulação do Joelho/cirurgia , Joelho , Fenômenos Biomecânicos , Amplitude de Movimento Articular , Ligamentos Colaterais/cirurgiaRESUMO
Introduction: Adequate bone quality is essential for long term biologic fixation of cementless total knee arthroplasty (TKA). Recently, vertebral bone quality evaluation using dual-energy computed tomography (DECT) has been introduced. However, the DECT bone mineral density (BMD) in peripheral skeleton has not been correlated with Hounsfield units (HU) or central dual-energy X-ray absorptiometry (DXA), and the accuracy remains unclear. Materials and methods: Medical records of 117 patients who underwent TKA were reviewed. DXA was completed within three months before surgery. DECT was performed with third-generation dual source CT in dual-energy mode. Correlations between DXA, DECT BMD and HU for central and periarticular regions were analyzed. Receiver operating characteristic (ROC) curves were plotted and area under the curve (AUC), optimal threshold, and sensitivity and specificity of each region of interest (ROI) were calculated. Results: Central DXA BMD was correlated with DECT BMD and HU in ROIs both centrally and around the knee (all p < 0.01). The diagnostic accuracy of DECT BMD was higher than that of DECT HU and was also higher when the T-score for second lumbar vertebra (L2), rather than for the femur neck, was used as the reference standard (all AUC values: L2 > femur neck; DECT BMD > DECT HU, respectively). Using the DXA T-score at L2 as the reference standard, the optimal DECT BMD cut-off values for osteoporosis were 89.2 mg/cm3 in the distal femur and 78.3 mg/cm3 in the proximal tibia. Conclusion: Opportunistic volumetric BMD assessment using DECT is accurate and relatively simple, and does not require extra equipment. DECT BMD and HU are useful for osteoporosis screening before cementless TKA.
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Densidade Óssea , Osteoporose , Absorciometria de Fóton/métodos , Colo do Fêmur , Humanos , Vértebras Lombares , Osteoporose/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1ß, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.
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Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/efeitos adversos , Imunidade/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prurido/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Quimiocinas/metabolismo , Dermatite Atópica/metabolismo , Proteínas Filagrinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Proteínas de Membrana/farmacologia , Camundongos , Precursores de Proteínas/farmacologia , Prurido/metabolismo , Pele/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
BACKGROUND/AIMS: Teeth in a jaw fracture line, because of the presence of the periodontal ligament, may communicate with the oral cavity. There are no guidelines for the management of teeth in mandibular fracture lines. The aim of this study was to investigate the factors related to dental problems with teeth involved in mandibular fracture lines and to determine the best treatment option. MATERIAL AND METHODS: This retrospective study was based on the medical and radiographic records of patients with mandibular fractures. The relationships among the patient's age, gender, smoking history, amount of bony displacement, surgery, trauma-surgery period, apical involvement, tooth mobility, and periodontal status were investigated. Group comparisons were performed using the chi-squared test, Fisher's exact test, and Mann-Whitney U-test. RESULT: A total of 238 patients (247 fracture lines) with mandibular fractures including a tooth in the line of the fracture were examined. Post-operative dental complications occurred in 42 cases (17.0%). Extraction of related teeth occurred in 34 cases (80.9%) compared to eight cases (19.0%) related to root canal therapy. This study defined "dental problem" as "a case with a tooth extracted or endodontically treated after trauma." The variables associated with an increased risk of dental problems were the amount of bony displacement (p < .01), tooth mobility (p < .01), and pre-existing marginal alveolar bone loss (p = .027). CONCLUSION: The prognosis of teeth in mandibular fracture lines was related to tooth mobility, periodontal state, and the amount of bony displacement.
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Fraturas Mandibulares , Fraturas dos Dentes , Mobilidade Dentária , Dente , Humanos , Fraturas Mandibulares/complicações , Fraturas Mandibulares/diagnóstico por imagem , Prognóstico , Estudos RetrospectivosRESUMO
The medicinal plant noni (Morinda citrifolia) is widely dispersed throughout Southeast Asia, the Caribbean, and Australia. We previously reported that fermented Noni could alleviate atopic dermatitis (AD) by recovering Th1/Th2 immune balance and enhancing skin barrier function induced by 2,4-dinitrochlorobenzene. Noni has a high deacetylasperulosidic acid (DAA) content, whose concentration further increased in fermented noni as an iridoid constituent. This study aimed to determine the anti-AD effects and mechanisms of DAA on HaCaT, HMC-1, and EOL-1 cells. DAA inhibited the gene expression and secretion of AD-related cytokines and chemokines including interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-25, IL-33, thymic stromal lymphopoietin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation, normal T cell expressed and secreted, in all cells, and inhibited histamine release in HMC-1 cells. DAA controlled mitogen-activated protein kinase phosphorylation levels and the translocation of nuclear factor-kappa light chain enhancer of activated B cells into the nucleus by inhibiting IκBα decomposition in all the cells. Furthermore, DAA increased the expression of proteins involved in skin barrier functions such as filaggrin and involucrin in HaCaT cells. These results confirmed that DAA could relieve AD by controlling immune balance and recovering skin barrier function.
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Dermatite Atópica/tratamento farmacológico , Glicosídeos/farmacologia , Linhagem Celular , Quimiocinas/imunologia , Quimiocinas/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Dermatite Atópica/patologia , Eczema/tratamento farmacológico , Eczema/patologia , Proteínas Filagrinas , Glicosídeos/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Morinda/metabolismo , Extratos Vegetais/farmacologia , Pele/metabolismo , Equilíbrio Th1-Th2/efeitos dos fármacosRESUMO
Connective tissue growth factor (CTGF), an extracellular matrix protein with various biological functions, is known to be upregulated in multiple chronic diseases such as liver fibrosis and congestive heart failure, but the mechanism it undertakes to cause alveolar bone loss in periodontitis remains elusive. The present study therefore investigates the pathways involving CTGF in chronic periodontitis. RNA sequencing revealed a notable increase in the expression of CTGF in chronic periodontitis tissues. Also, TRAP staining, TRAP activity and bone resorption assays showed that osteoclast formation and function is significantly facilitated in CTGF-treated bone marrow-derived macrophages (BMMs). Interestingly, western blotting and immunofluorescence staining results displayed that CTGF had little effect on the osteoclastogenic differentiation mediated by the positive regulators of osteoclastogenesis such as nuclear factor of activated T cells 1 (NFATc1). However, following results showed that both the mRNA and protein expressions of B cell lymphoma 6 (Bcl6), a transcriptional repressor of "osteoclastic" genes, were significantly downregulated by CTGF treatment. Moreover, CTGF upregulated the expressions of v-ATPase V0 subunit d2 (ATP6v0d2) and Dendritic cell-specific transmembrane protein (DC-STAMP) which are osteoclastic genes specifically required for osteoclast cell-cell fusion in pre-osteoclasts. Findings from this study suggest that CTGF promotes the fusion of pre-osteoclasts by downregulating Bcl6 and subsequently increasing the expression of DC-STAMP in periodontitis. Understanding this novel mechanism that leads to increased osteoclastogenesis in periodontitis may be employed for the development of new therapeutic targets for preventing periodontitis-associated alveolar bone resorption.
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Perda do Osso Alveolar/etiologia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Osteogênese , Periodontite/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Perda do Osso Alveolar/metabolismo , Animais , Estudos de Casos e Controles , Feminino , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Osteoclastos/metabolismo , Periodontite/complicaçõesRESUMO
Letrozole is a reversible nonsteroidal aromatase inhibitor that is widely used in postmenopausal breast cancer patients. It is well established that letrozole decreases bone density owing to estrogen depletion; however, few studies have reported its direct effect on bone cells in vitro. Therefore, we investigated the effect of letrozole on bone metabolism, focusing on osteoclastogenesis. Letrozole did not affect the viability, proliferation, or migration of bone marrow-derived macrophages (BMMs); however, it reduced the multinucleation of immature osteoclasts and subsequent bone resorption in vitro. Overall, letrozole inhibited the expression of dendritic cell-specific transmembrane protein (DC-STAMP), tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K. Among them, the reduced expression of DC-STAMP was the most prominent. However, this downregulation of DC-STAMP expression following letrozole treatment was not related to the inhibition of major osteoclastogenesis pathways, such as the nuclear factor-κB (NF-κB), c-Fos, and nuclear factor of activated T cell c1 (NFATc1) pathways, but was attributed to the inhibition of p38, which is known to reside upstream of DC-STAMP expression. Notably, the anti-osteoclastogenic effect of letrozole was abolished following treatment with the p38 activator anisomycin. Contrary to our expectations, these results strongly suggest a previously unknown anti-osteoclastogenic activity of letrozole, mediated by the downregulation of the p38/DC-STAMP pathway.
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Células Dendríticas/efeitos dos fármacos , Letrozol/farmacologia , Proteínas de Membrana/metabolismo , Osteoclastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Fusão Celular/métodos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
Chemotherapy is not a first-line therapy for oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer, because most OSCC shows resistance to chemotherapeutic reagents. Inflammatory signals are suggested to be associated with chemoresistance as well as carcinogenesis in many different cancers, and thus chronic periodontitis, the most common chronic inflammatory disease of the oral cavity, could modulate responsiveness to chemotherapeutic agents used against oral cancer. This study was performed to define the role of chronic periodontitis in oral cancer progression and to determine the responsiveness of oral cancer to a chemotherapeutic reagent. First, we quantified the tumor growth rate and changes in serum cytokine profiles of mice administered Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Compared with uninfected mice, the mice that were chronically administered P. gingivalis showed increased resistance to paclitaxel and a decreased tumor growth rate. In addition, P. gingivalis-treated mice exhibited higher serum levels of interleukin-6 (IL-6) than uninfected mice. Furthermore, the sensitivity of tumor xenografts to paclitaxel in mice administered P. gingivalis was dramatically increased when the mice were administered ibuprofen, an anti-inflammatory drug which supports the modulatory effect of periodontal pathogen-induced inflammation in chemoresistance.
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Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/fisiopatologia , Resistencia a Medicamentos Antineoplásicos , Inflamação/complicações , Porphyromonas gingivalis/imunologia , Administração Oral , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/microbiologia , Linhagem Celular Tumoral , Humanos , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Masculino , Camundongos , Paclitaxel/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
It has been suggested that Porphyromonas gingivalis (P. gingivalis), a keystone pathogen in chronic periodontitis, is associated with a variety of cancers, including oral cancer. Recently, studies have shown the effects of persistent exposure to P. gingivalis on the promotion of tumorigenic properties of oral epithelial cells, suggesting that chronic P. gingivalis infection is a potential risk factor for oral cancer. On the other hand, Fusobacterium nucleatum (F. nucleatum), one of the major periodontal pathogens, has emerged as an important factor in the colon cancer progression. Here, we investigated the diagnostic potential of serum immunoglobulin G antibody against periodontal pathogens, P. gingivalis and F. nucleatum, and serum IL-6 for oral squamous cell carcinoma (OSCC). An enzyme-linked immunosorbent assay (ELISA) was used to determine and compare the serum levels of interleukin 6 (IL-6), F. nucleatum IgG, and P. gingivalis IgG in 62 OSCC patients with 46 healthy controls. The serum levels of P. gingivalis IgG and IL-6 were higher in OSCC patients than in non-OSCC controls, and the difference was statistically significant. In addition, a high serum level of IL-6 was associated with a worse prognosis in OSCC patients. Thus, P. gingivalis IgG and IL-6 could be utilized as potential serum biomarkers for the diagnosis of OSCC, and the serum level of IL-6 contributes to improved prognostic performance.
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Anticorpos Antibacterianos/imunologia , Biomarcadores , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/metabolismo , Interleucina-6/sangue , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , Porphyromonas gingivalis/imunologia , Anticorpos Antibacterianos/sangue , Infecções por Bacteroidaceae/microbiologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Curva ROCRESUMO
Melatonin has anabolic effects on the bone, even under hypoxia, and laser irradiation has been shown to improve osteoblastic differentiation. The aim of this study was to investigate whether laser irradiation and melatonin would have synergistic effects on osteoblastic differentiation and mineralization under hypoxic conditions. MC3T3-E1 cells were exposed to 1% oxygen tension for the hypoxia condition. The cells were divided into four groups: G1-osteoblast differentiation medium only (as the hypoxic condition), G2-treatment with 50 µM melatonin only, G3-laser irradiation (808 nm, 80 mW, GaAlAs diode) only, and G4-treatment with 50 µM melatonin and laser irradiation (808 nm, 80 mW, GaAlAs diode). Immunoblotting showed that osterix expression was markedly increased in the melatonin-treated and laser-irradiated cells at 48 and 72 h. In addition, alkaline phosphatase activity significantly increased and continued to rise throughout the experiment. Alizarin Red staining showed markedly increased mineralized nodules as compared with only melatonin-treated or laser-irradiated cells at day 7, which significantly increased by day 14. Moreover, when melatonin-treated cells were laser-irradiated, the differentiation and mineralization of cells were found to involve p38 MAPK and PRKD1 signaling mechanisms. However, the enhanced effects of laser irradiation with melatonin were markedly inhibited when the cells were treated with luzindole, a selective melatonin receptor antagonist. Therefore, we concluded that laser irradiation could promote the effect of melatonin on the differentiation and mineralization of MC3T3-E1 cells under hypoxic conditions, and that this process is mediated through melatonin 1/2 receptors and PKRD/p38 signaling pathways.
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Regeneração Óssea/fisiologia , Hipóxia/fisiopatologia , Lasers Semicondutores/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Melatonina/uso terapêutico , Osteoblastos/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Terapia Combinada , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/efeitos da radiação , Osteogênese/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
In vertebrates, melatonin is primarily secreted from the pineal gland but it affects various biological processes including the sleep-wake cycle, vasomotor control, immune system and bone homeostasis. Melatonin has been known to promote osteoblast differentiation and bone maturation, but a direct role of melatonin on osteoclast differentiation is still elusive. The present study investigated the effect of melatonin on the differentiation of macrophages to osteoclasts. The presence of melatonin significantly reduced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and the siRNA-mediated knockdown of the melatonin receptor failed to overcome the anti-osteoclastogenic effect of melatonin. Although melatonin treatment did not affect the phosphorylation of extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), it markedly inhibited the activation of NF-κB and subsequent induction of nuclear factor of activated T cell cytoplasmic 1(NFATc1). Thus, our results suggest that melatonin could suppress osteoclast differentiation through downregulation of NF-κB pathway with concomitant decrease in the NFATc1 transcription factor induction. Furthermore, melatonin seems to have an anti-osteoclastogenic effect independent of plasma membrane melatonin receptors. In addition to previously reported properties of melatonin, our study proposes another aspect of melatonin and bone homeostasis.
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Reabsorção Óssea/metabolismo , Melatonina/metabolismo , Osteoclastos/metabolismo , Animais , Reabsorção Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Expressão Gênica , Inativação Gênica , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Ligante RANK/metabolismo , Receptores de Melatonina/genética , Receptores de Melatonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
Recent studies indicate that chronic inflammation promotes the aggressiveness of cancers. However, the direct molecular mechanisms underlying a functional link between chronic periodontitis, the most common form of oral inflammatory diseases, and the malignancy of oral cancer remain unknown. To elucidate the role of chronic periodontitis in progression of oral cancer, we examined the effect of Porphyromonas gingivalis (P. gingivalis), a major pathogen that causes chronic periodontitis, on the invasiveness of oral squamous cell carcinoma (OSCC) cells, including SCC-25, OSC-20 and SAS cells. Exposures to P. gingivalis promoted the invasive ability of OSC-20 and SAS cells via the upregulation of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-2. However, P. gingivalis-infected SCC-25 cells did not exhibit changes in their invasive properties or the low expression levels of MMPs. In an effort to delineate the molecular players that control the invasiveness, we first assessed the level of interleukin-8 (IL-8), a well-known inflammatory cytokine, in P. gingivalis-infected OSCC cells. IL-8 secretion was substantially increased in the OSC-20 and SAS cells, but not in the SCC-25 cells, following P. gingivalis infection. When IL-8 was directly applied to SCC-25 cells, their invasive ability and MMP level were significantly increased. Furthermore, the downregulation of IL-8 in P. gingivalis-infected OSC-20 and SAS cells attenuated their invasive potentials and MMP levels. Taken together, our findings strongly suggest that P. gingivalis infection plays an important role in the promotion of the invasive potential of OSCC cells via the upregulation of IL-8 and MMPs.
Assuntos
Carcinoma de Células Escamosas/patologia , Interleucina-8/genética , Metaloproteinases da Matriz/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica , Porphyromonas gingivalis/fisiologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/microbiologia , Linhagem Celular Tumoral , Humanos , Interleucina-8/imunologia , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
BACKGROUND: Ischemia-reperfusion of bone occurs in a variety of clinical conditions, such as orthopedic arthroplasty, plastic gnathoplasty, spinal surgery, and amputation. Usually, cellular models of hypoxia-reoxygenation reflect in vivo models of ischemia-reperfusion. With respect to hypoxia-reoxygenation conditions, the effects of remifentanil on osteogenesis have received little attention. Therefore, we investigated the effects of remifentanil on the proliferation and differentiation of osteoblasts during hypoxic-reoxygenation. METHODS: After remifentanil (0.1, 1 ng/mL) preconditioning for 2 hours, human osteoblasts were cultured under 1% oxygen tension for 24 hours. Thereafter, the cells were reoxygenated for 12 hours at 37 °C. The naloxone groups were treated with naloxone for 30 minutes before remifentanil treatment. We measured cell viability via MTT assay. Osteoblast maturation was determined by assay of bone nodular mineralization. Quantitative PCR and western blot methods were used to determine BMP-2, osteocalcin, Akt, type I collagen, osterix, TGF-ß1, HIF-1α, and RUNX2 expression levels. RESULTS: Osteoblast viability and bone nodular mineralization by osteoblasts is recovered by remifentanil preconditioning from hypoxia-reoxygenation insult. During hypoxic-reoxygenation condition, remifentanil preconditioning induced the expression of BMP-2, osteocalcin, Akt, type I collagen, osterix, TGF-ß1, HIF-1α, and RUNX2 in osteoblasts. CONCLUSIONS: Under hypoxia-reoxygenation conditions, remifentanil preconditioning enhanced the cell viability and maturation of osteoblasts, and stimulated the expression of proteins associated with osteoblast proliferation and differentiation of the osteoblast. Our results suggest that remifentanil may help in the treatment of bone stress injuries.
Assuntos
Proliferação de Células/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Piperidinas/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/lesões , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Naloxona/administração & dosagem , Osteogênese/efeitos dos fármacos , Oxigênio/metabolismo , Remifentanil , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologiaRESUMO
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy. However, its pathophysiology is not yet fully elucidated, and effective treatment of BRONJ remains unclear. The aim of this study is to investigate the effects of alendronate on oral keratinocytes and of low-level laser therapy (LLLT) on alendronate-treated keratinocytes, specifically by evaluating their viability, apoptosis, and wound healing function after irradiation. Oral keratinocyte cells (HaCaT) were exposed to 25 µM alendronate. Then, laser irradiation was performed with a low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; NDLux, Seoul, Korea) using 1.2 J/cm(2) energy dose. Viability was analyzed using MTT assay. Apoptosis was measured by Hoechst staining, caspase assay. Changes in secretion of IL-8, VEGF, and collagen type I were studied by ELISA and immunofluorescence microscopy. Scratch wound assays were also performed to measure cellular migration. Our results show that alendronate inhibits keratinocyte viability, expression of IL-8, VEGF, and collagen type I which are intimately related to healing events and cell migration while promoting apoptosis. Our results serve to demonstrate the utility of LLLT in partially overcoming the inhibitory effects of this bisphosphonate. From these results, the authors believe that the present study will provide an experimental basis for a fuller explanation of the clinical effects of LLLT as a BRONJ treatment modality.
Assuntos
Difosfonatos/química , Queratinócitos/efeitos dos fármacos , Terapia com Luz de Baixa Intensidade/métodos , Cicatrização/efeitos dos fármacos , Alendronato/química , Apoptose/efeitos dos fármacos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Colágeno Tipo I/metabolismo , Humanos , Interleucina-8/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Osteoblastic differentiation and bone-forming capacity are known to be suppressed under hypoxic conditions. Melatonin has been shown to influence cell differentiation. A number of in vitro and in vivo studies have suggested that melatonin also has an anabolic effect on bone, by promoting osteoblastic differentiation. However, the precise mechanisms and the signaling pathways involved in this process, particularly under hypoxic conditions, are unknown. This study investigated whether melatonin could promote osteoblastic differentiation and mineralization of preosteoblastic MC3T3-E1 cells under hypoxic conditions. Additionally, we examined the molecular signaling pathways by which melatonin mediates this process. We found that melatonin is capable of promoting differentiation and mineralization of MC3T3-E1 cells cultured under hypoxic conditions. Melatonin upregulated ALP activity and mRNA levels of Alp, Osx, Col1, and Ocn in a time- and concentration-dependent manner. Alizarin red S staining showed that the mineralized matrix in hypoxic MC3T3-E1 cells formed in a manner that was dependent on melatonin concentration. Moreover, melatonin stimulated phosphorylation of p38 Mapk and Prkd1 in these MC3T3-E1 cells. We concluded that melatonin promotes osteoblastic differentiation of MC3T3-E1 cells under hypoxic conditions via the p38 Mapk and Prkd1 signaling pathways.
Assuntos
Antioxidantes/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Melatonina/farmacologia , Osteoblastos/efeitos dos fármacos , Animais , Western Blotting , Hipóxia Celular/fisiologia , Linhagem Celular , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Proteína Quinase C/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: The purpose of this study was to investigate which factors affect upper dental midline deviation in dentofacial deformity patients using cone-beam computed tomography analysis. PATIENTS AND METHODS: Twenty-eight patients were selected for this study. Subjects were divided into 2 groups according to the amount of upper incisor (U1) midline deviation from the clinical facial midline: group 1 (U1 deviation <2 mm) and group 2 (U1 deviation >2 mm). Linear measurements, angles, and reference planes on 3-dimensional (3D) computed tomograms were obtained. The predictor variables were maxillary yaw, palatal plane angle, differences of maxillary point to the coronal and sagittal planes, and maxillary canting. The outcome variable was U1 deviation. The variables between the 2 groups and 2 sides were analyzed with a t test. Pearson correlation coefficient and multiple regression analysis were also calculated within each group for each measurement against the U1 deviation to determine which variables affect U1 deviation. P < .05 was considered statistically significant. RESULTS: The patients were evenly distributed between each group (n = 14 in each group). There was significant deviation of U1 from the sagittal plane in group 2 compared with group 1 (0.99 mm in group 1 vs 1.73 mm in group 2, P < .05). When we compared yaw with the sagittal plane, group 2 was more rotated than group 1 (1.16° in group 1 vs 2.28° in group 2, P < .01). Through multiple regression analysis, the primary predictor variable for U1 deviation was maxillary yaw (P < .05). CONCLUSIONS: This study suggests that maxillary yaw is the primary contributing factor for upper dental midline deviation. The use of maxillary yaw should be considered when one is performing orthognathic surgery in patients with U1 deviation to achieve optimum esthetics.
Assuntos
Cefalometria , Tomografia Computadorizada de Feixe Cônico , Assimetria Facial/diagnóstico por imagem , Imageamento Tridimensional/métodos , Má Oclusão/patologia , Maxila/patologia , Adulto , Pontos de Referência Anatômicos , Cefalometria/estatística & dados numéricos , Arco Dental/patologia , Feminino , Humanos , Incisivo , Masculino , Maxila/diagnóstico por imagem , Procedimentos Cirúrgicos Ortognáticos , Valor Preditivo dos Testes , Análise de Regressão , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto JovemRESUMO
The aim of this study was to examine the effect of low-level laser therapy (LLLT) on the cell viability and the expression of hypoxia-inducible factor-1s (HIF-1s), bone morphogenic protein-2 (BMP-2), osteocalcin, type I collagen, transforming growth factor-ß1 (TGF-ß1), and Akt in hypoxic-cultured human osteoblasts. Human fetal osteoblast cells (cell line 1.19) were cultured under 1 % oxygen tension for 72 h. Cell cultures were divided into two groups. At the experimental side, low-level laser (808 nm, GaAlAs diode) was applied at 0, 24, and 48 h. After irradiation, each cell culture was incubated 24 h more under hypoxia. Total energy was 1.2, 2.4, and 3.6 J/cm(2), respectively. Non-irradiated cultures served as controls. Comparisons between the two groups were analyzed by t test; a p value <0.05 was considered statistically significant. Hypoxia resulted in a decrease in the expression of type I collagen, osteocalcin, and TGF-ß1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Cell viability and BMP-2 expression were not decreased by hypoxic condition. On the other hand, LLLT on hypoxic-cultured osteoblast promoted the expression of BMP-2, osteocalcin, and TGF-ß1 (p < 0.05, p < 0.01, and p < 0.001, respectively). Cell proliferation was also increased time-dependently. However, hypoxia decreased in type I collagen expression (p < 0.001), and LLLT did not affect type I collagen expression in hypoxic-cultured osteoblasts. Furthermore, LLLT inhibited HIF-1 and Akt expression in hypoxic conditioned osteoblasts. We concluded that LLLT induces the expression of BMP-2, osteocalcin, and TGF- ß1 in 1 % hypoxic-cultured human osteoblasts.
Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Terapia com Luz de Baixa Intensidade , Osteoblastos/metabolismo , Osteoblastos/efeitos da radiação , Osteocalcina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Hipóxia Celular , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Colágeno Tipo I/metabolismo , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Osteocalcina/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta1/genéticaRESUMO
(1) Background: A cementless total knee arthroplasty (TKA) is a recent and an increasingly popular innovation that enhances porous fixation surfaces. However, the lack of cemented sealing of an exposed resected bone has raised concerns about the potential for greater blood loss. The goals of this study were to determine if a cementless approach impacts post-TKA hemodynamics and to identify risk factors for blood loss in instances of cementless (vs. cemented) TKAs under a contemporary patient blood management (PBM) protocol. (2) Methods: We recruited 153 consecutive patients undergoing unilateral TKAs between 2019 and 2023. All enrollees received cementless or cemented prostheses of the same design (cementless, 87; cemented, 66). After propensity score matching for demographics, there were 46 patients in each group. We then compared blood loss metrics (total [TBL] and estimated [EBL]), drainage volumes, hemoglobin (Hb) levels, and transfusion rates by group. (3) Results: Post-TKA hemodynamics (i.e., TBL, EBL, drainage, Hb level, and transfusion rate) of cementless (n = 46) and cemented (n = 46) TKA groups did not differ significantly. In addition, the proportions of patients with Hb drops > 3.0 g/dL were similar for the two groups. A logistic regression analysis revealed that only preoperative Hb and EBL during the early postoperative period were predictive of a substantial fall in Hb levels. The fixation method was not associated with Hb decline > 3.0 g/dL by postoperative Day 3. (4) Conclusion: The cementless TKA has no impact on customary post-TKA hemodynamics and is not associated with greater TKA-related blood loss when implementing a contemporary PBM protocol.