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Extracellular vesicles (EVs) play crucial roles in physiological and pathophysiological processes. Although studies have described muscle-bone interactions via humoral factors, we reported that EVs from C2C12 muscle cells (Myo-EVs) suppress osteoclast formation. Current clinical evidence suggests that inflammation induces both sarcopenia and osteoporosis. Although tumor necrosis factor-α (TNF-α) is a critical proinflammatory factor, the influences of TNF-α on muscle-bone interactions and Myo-EVs are still unclear. In the present study, we investigated the effects of TNF-α stimulation of C2C12 cells on osteoclast formation and osteoblastic differentiation modulated by Myo-EVs in mouse cells. TNF-α significantly decreased the protein amount in Myo-EVs, but did not affect the Myo-EV size distribution. TNF-α treatment of C2C12 myoblasts significantly decreased the suppression of osteoclast formation induced by Myo-EVs from C2C12 myoblasts in mouse bone marrow cells. Moreover, TNF-α treatment of C2C12 myoblasts in mouse preosteoclastic Raw 264.7 cells significantly limited the Myo-EV-induced suppression of osteoclast formation and decreased the Myo-EV-induced increase in mRNA levels of osteoclast formation-related genes. On the other hand, TNF-α treatment of C2C12 muscle cells significantly decreased the degree of Myo-EV-promoted mRNA levels of Osterix and osteocalcin, as well as ALP activity in mouse mesenchymal ST-2 cells. TNF-α also significantly decreased miR196-5p level in Myo-EVs from C2C12 myoblasts in quantitative real-time PCR. In conclusion, TNF-α stimulation of C2C12 muscle cells blunts both the osteoclast formation suppression and the osteoblastic differentiation promotion that occurs due to Myo-EVs in mouse cells. Thus, TNF-α may disrupt the muscle-bone interactions by direct Myo-EV modulation.
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Vesículas Extracelulares , MicroARNs , Animales , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Diferenciación Celular , Células Musculares , Vesículas Extracelulares/metabolismo , ARN Mensajero/metabolismo , MicroARNs/metabolismoRESUMEN
Exercise is important for the prevention and treatment of sarcopenia and osteoporosis. Although the interactions between skeletal muscles and bone have recently been reported, the myokines linking muscle to bone during exercise remain unknown. We previously revealed that chronic exercise using treadmill running blunts ovariectomy-induced osteopenia in mice. We herein performed an RNA sequence analysis of the gastrocnemius and soleus muscles of male mice with or without chronic exercise to identify the myokines responsible for the effects of chronic exercise on the muscle/bone relationship. We extracted peripheral myelin protein 22 (PMP22) as a humoral factor that was putatively induced by chronic exercise in the soleus and gastrocnemius muscles of mice from the RNA sequence analysis. Chronic exercise significantly enhanced the expression of PMP22 in the gastrocnemius and soleus muscles of female mice. PMP22 suppressed macrophage-colony stimulating factor and receptor activator factor κB ligand-induced increases in the expression of osteoclast-related genes and osteoclast formation from mouse bone marrow cells. Moreover, PMP22 significantly inhibited osteoblast differentiation, alkaline phosphatase activity, and mineralization in mouse osteoblast cultures; however, the overexpression of PMP22 did not affect muscle phenotypes in mouse muscle C2C12 cells. A simple regression analysis revealed that PMP22 mRNA levels in the gastrocnemius and soleus muscles were positively related to cortical bone mineral density at the femurs of mice with or without chronic exercise. In conclusion, we identified PMP22 as a novel myokine induced by chronic exercise in mice. We first showed that PMP22 suppresses osteoclast formation and the osteoblast phenotype in vitro.
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Enfermedades Óseas Metabólicas , Huesos , Proteínas de la Mielina/metabolismo , Animales , Enfermedades Óseas Metabólicas/metabolismo , Huesos/metabolismo , Femenino , Masculino , Ratones , Músculo Esquelético/metabolismo , Osteoclastos/metabolismoRESUMEN
INTRODUCTION: Irisin is a proteolytic product of fibronectin type II domain-containing 5, which is related to the improvement in glucose metabolism. Numerous studies have suggested that irisin is a crucial myokine linking muscle to bone in physiological and pathophysiological states. MATERIALS AND METHODS: We examined the effects of local irisin administration with gelatin hydrogel sheets and intraperitoneal injection of irisin on the delayed femoral bone repair caused by streptozotocin (STZ)-induced diabetes in female mice. We analyzed the femurs of mice using quantitative computed tomography and histological analyses and then measured the mRNA levels in the damaged mouse tissues. RESULTS: Local irisin administration significantly blunted the delayed bone repair induced by STZ 10 days after a femoral bone defect was generated. Local irisin administration significantly blunted the number of Osterix-positive cells that were suppressed by STZ at the damaged site 4 days after a femoral bone defect was generated, although it did not affect the mRNA levels of chondrogenic and adipogenic genes 4 days after bone injury in the presence or absence of diabetes. On the other hand, intraperitoneal injection of irisin did not affect delayed bone repair induced by STZ 10 days after bone injury. Irisin significantly blunted the decrease in Osterix mRNA levels induced by advanced glycation end products or high-glucose conditions in ST2 cells in the presence of bone morphogenetic protein-2. CONCLUSIONS: We first showed that local irisin administration with gelatin hydrogel sheets improves the delayed bone repair induced by diabetic state partially by enhancing osteoblastic differentiation.
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Diabetes Mellitus Experimental , Fibronectinas , Animales , Huesos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/genética , Femenino , Fibronectinas/genética , Fibronectinas/metabolismo , Fibronectinas/farmacología , Gelatina , Hidrogeles , Ratones , ARN Mensajero/genéticaRESUMEN
A 68-year-old woman presenting with anorexia and epigastric pain was diagnosed with metastatic pancreatic cancer and idiopathic thrombocytopenic purpura(ITP). Chemotherapy was initiated with S-1. Subsequently, gemcitabine was administered in combination with prednisolone. Her platelets returned to normal after the treatment with steroids and chemotherapy, but the treatment could not be withdrawn completely. Pancreatic cancer presenting as idiopathic thrombocytopenic purpura has rarely been reported in the literature. Here, we present our experience and discuss a case of pancreatic cancer complicated with ITP.
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Neoplasias Pancreáticas , Púrpura Trombocitopénica Idiopática , Anciano , Femenino , Humanos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/tratamiento farmacológico , Prednisolona , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológicoRESUMEN
Background: Most cancers are lifestyle-related and are thus preventable. Lifestyle habits can be improved by individual efforts; for example, because oral health is suggested to play a preventive role in cancer risk, toothbrushing is considered a critical and fundamental measure for controlling oral health. This study aimed to investigate the association between toothbrushing and cancer risk. Methods: Cross-sectional data from the Japan COVID-19 and Society Internet Survey, a large-scale (n = 32,000) online survey conducted in 2022, were used. From September 12 to October 19, 2022, questionnaires were distributed to candidates selected by simple random sampling from a Japanese Internet research company's panelists to represent the Japanese population. The association between toothbrushing and cancer risk according to cancer prevalence was then analyzed. Results: Among all 32,000 participants, 2,495 (7.8%) who had any cancer previously were analyzed. Multivariable logistic regression analysis revealed a significant association between toothbrushing habit and cancer risk. Conclusion: The findings of this study suggest that daily toothbrushing is essential for maintaining oral health and preventing cancer.
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PURPOSE: During the Coronavirus Disease 2019 (COVID-19) pandemic, there has been concern about nosocomial infections acquired through dental practice, where machines - such as air turbines - that generate aerosols are used, and where there are many opportunities to come into contact with saliva and blood. Because there is no report to date on whether dental treatment is associated with a risk of SARS-CoV-2 infection in Japan, the aim of the present cross-sectional study was to examine the risk of SARS-CoV-2 infection associated with dental treatment. MATERIALS AND METHODS: Cross-sectional data were gathered from the Japan COVID-19 and Society Internet Survey (JACSIS), a large-scale internet survey conducted in 2021 (n=28,175). From September 27, 2021, to October 30, 2021, the questionnaires were distributed to candidates selected from the panelists of a Japanese Internet research company to represent the Japanese population regarding age, sex, and residential prefecture using a simple random sampling procedure. The risk of SARS-CoV-2 infection related to dental treatment was examined and analysed. RESULTS: Multivariable logistic regression analysis showed that younger age, male sex and living alone were statistically significant factors positively associated with SARS-CoV-2 infection, whereas the presence or absence of dental treatment was not statistically significantly correlated with SARS-CoV-2 infection. CONCLUSION: The present epidemiological study showed that dental treatment is not a positive risk factor for SARS-CoV-2 infection in Japan.
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COVID-19 , Infección Hospitalaria , Humanos , Masculino , COVID-19/epidemiología , Estudios Transversales , Japón/epidemiología , SARS-CoV-2RESUMEN
Aims Since it is known that oral problems affect various medical diseases, the effects of restrictions on visits for dental treatment on exacerbations of various systemic medical diseases were examined.Method and materials The data were used from the Japan COVID-19 and Society Internet Survey, a large-scale internet survey conducted in 2021 (n = 28,175). The questionnaires were distributed to 33,081 candidates who were selected to represent the Japanese population regarding age, sex and residential prefecture using a simple random sampling procedure. Patients currently undergoing treatment for diabetes mellitus, hypertension, asthma, cardiocerebrovascular disease, hyperlipidemia, atopic dermatitis, and mental illness, such as depression, were extracted from the total participants. Then, whether discontinuation of dental treatment affected the exacerbation of their systemic disease was examined.Results Overall, 50-60% of patients with each systemic disease had continued to receive dental treatment, and 4-8% of them had discontinued dental treatment. On univariate and multivariate analyses, discontinuation of dental treatment is a risk factor in the exacerbation of diabetes mellitus, hypertensive conditions, asthma, cardiocerebrovascular disease and hyperlipidemia.Conclusion The present epidemiological study showed the relationship between oral health and systemic health, which can provide meaningful insights regarding future medical-dental collaboration in Japan.