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Fire is an important ecological disturbance, but anthropogenic wildfires increasingly threaten native ecosystems and human lives. In fire-prone ecosystems, zero-fire policies have been replaced by active fire management to reduce the risk of wildfires and improve ecological outcomes. The environmental drivers of fire behavior are widely known, but climate change and deforestation are changing their roles, making fires less predictable. Thus, reassessing the main determinants of fire behavior is preeminent to allow for safe and adaptive uses of fire in protected areas (PA). We did this research in collaboration with PA managers during the initial implementation of a pilot Integrated Fire Management (IFM) program in the Brazilian savanna. The program mainly aimed to prevent large wildfires in the late-dry season and included prescribed burns during the rainy, early- and mid-dry seasons to create vegetation patch mosaics with different fire histories. We assessed fire behavior and its environmental drivers during prescribed fires in the mid-dry season (MF) and experimental late-dry season fires (LF) (emulating wildfires). We applied Linear Models to test for differences in fire intensity, heat released, combustion factor and flame height between fire seasons and to check the influence of meteorological and fuel conditions in these parameters. LF had a significantly higher fire intensity (3508 vs. 895 kW m-1), heat released (5537 vs. 3329 kW m-2), combustion factor (90 vs. 51%) and flame height (2.5 vs. 1.9 m) than MF. Relative humidity, air temperature, wind speed and fuel load were the best predictors of fire behavior, corroborating previous research. Air temperature and relative humidity pushed the seasonal differences in fire behavior while wind speed and fuel load showed similar effects across seasons. Our results emphasize the importance of considering primarily environmental variables during fire management planning, especially in the current climate changing world where extreme events and seasonal weather fluctuations are constantly defying our knowledge about fire behavior.
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Ecossistema , Incêndios , Brasil , Pradaria , Humanos , Tempo (Meteorologia)RESUMO
INTRODUCTION: Some studies show that participants do not always fully understand the informed consent form (ICF), which is one of the reasons for dropouts. This study aimed to adapt the Quality of Informed Consent (QuIC) questionnaire into a valid instrument to be applied to the Portuguese population and to measure its reliability and validity in the Portuguese population, by applying it to a sample of participants in controlled trials. METHODS: The QuIC questionnaire was developed to assess the quality of informed consent in clinical trials and consists of two parts, addressing both the objective (part A) and the subjective (part B) understanding. After being translated and validated into Portuguese, it was implemented in 100 cardiac participants of phase III clinical trials in a University Hospital Center. RESULTS: The QuIC-PT questionnaire showed excellent stability over time and good validity. All patients evaluated their participation and their health positively and recognized the main purpose of the clinical trial. Almost all participants understood their role in helping future patients and the purpose of the trial and realized that, by signing the ICF, they were participating in a clinical trial. However, none of them knew that their experimental treatment was not proven to be the best alternative for their condition. CONCLUSION: The QuIC-PT questionnaire seems to be a valid and useful instrument to evaluate the participants' understanding of the ICF. In this study, we found that some concepts, like 'study protocol' or 'randomization', were not well understood by participants when signing the ICF, especially by participants with lower education levels. They also believed that the experimental intervention would solve their health condition. Greater awareness about the importance of the informed consent process and ICF is necessary so that participants can fully understand the protocol, especially the risks involved, and their rights as participants.
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Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of "smart" biomaterials.
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Transplante Ósseo , Cerâmica , Osteogênese , Animais , Materiais Biocompatíveis , Fosfatos de Cálcio/farmacologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Varredura , Osteogênese/efeitos dos fármacos , Ovinos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Transplante AutólogoRESUMO
Two groups of 8 individually housed young crossbred-bulls, in the finishing period, were used to test the effect of a Total Mixed Ration diet with high forage content (54% DM), low starch content (14% DM), supplemented with sunflower seeds (10% DM) (HFS) on growth performance, carcass and meat quality, fatty acid profile and carbon footprint, with reference to a conventional concentrate-based (90% DM) (Control) diet. The experiment lasted 64 days before slaughter. During the experiment, feed intake was monitored daily and live weight every 14 days. Individual CH4 emissions were assessed at 16-days intervals, using a GreenFeed for Large Animal unit. Feed intake and feed conversion ratio were higher for HFS diet, but average daily weight gain and feeding costs were similar for the two diets. Dressing percentage was reduced with HFS diet. The HFS increased redness, yellowness and Chroma of subcutaneous fat, but did not compromise commercial value of the carcasses. Meat colour, shear force, or sensory parameters were not affected by diet. The HFS diet allowed a healthier FA profile, due to the higher proportions of 18:3n-3, t11-18:1 and c9,t11-18:2 and the lower proportion of t10-18:1. The HFS diet did not reduce the carbon footprint in the finishing period of young bulls, due to increased digestive CH4 emissions. The results of this experiment showed that the HFS diet can be an alternative to the conventional diets used in finishing young-bulls. Although it may result in a slight reduction in animal performance, it has a strong impact on reducing dependence on inputs from outside the farm.
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Gases de Efeito Estufa , Animais , Bovinos , Masculino , Ração Animal/análise , Dieta/veterinária , Carne , Suplementos NutricionaisRESUMO
Dermatomyositis is an inflammatory disease that affects muscle strength and causes skin manifestations. There is an increased incidence of cancer in patients with this diagnosis although the pathophysiology of this association is still not completely understood. We report a case of a 65-year-old man who presented to the emergency department with proximal muscle weakness, weight loss, dysphagia, enlarged supraclavicular lymph nodes, an erythematous rash in the malar and supraciliary regions, and papules in the extensor metacarpophalangeal and interphalangeal joints. He had elevated creatine kinase and positive anti-nuclear matrix protein-2 autoantibodies. The skin and muscle biopsies performed confirmed the diagnosis of dermatomyositis. A thorough investigation seeking an associated condition was conducted and a prostate adenocarcinoma was diagnosed. The patient was treated with glucocorticoids and intravenous immune globulin with dysphagia and muscle weakness improvement and therefore allowing hospital discharge. He is currently undergoing oncologic treatment. Myositis-specific antibodies have proved to be extremely useful in the diagnosis, prognosis, and management of patients with dermatomyositis. Various phenotypes of the disease can associate differently with a systemic condition (namely a malignant disease). This case illustrates a rare form of cancer presentation that every clinician, especially those who work in the emergency room or in primary care and therefore have immediate contact with many patients, must be able to recognize.
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In the past thirty years, a number of biomaterials have shown the ability to induce bone formation when implanted at heterotopic sites, an ability known as osteoinduction. Such biomaterials--osteoinductive biomaterials--hold great potential for the development of new therapies in bone regeneration. Although a variety of well characterised osteoinductive biomaterials have so far been reported in the literature, scientists still lack fundamental understanding of the biological mechanism underlying the phenomenon by which they induce bone formation. This is further complicated by the observations that larger animal models are required for research, since limited, if any, bone induction by biomaterials is observed in smaller animals, including particularly rodents. Besides interspecies variation, variations among individuals of the same species have been observed. Furthermore, comparing different studies and drawing general conclusions is challenging, as these usually differ not only in the physico-chemical and structural properties of the biomaterials, but also in animal model, implantation site and duration of the study. Despite these limitations, the knowledge of material properties relevant for osteoinduction to occur has tremendously increased in the past decades. Here we review the properties of osteoinductive biomaterials, in the light of the model and the conditions under which they were tested. Furthermore, we give an insight into the biological processes governing osteoinduction by biomaterials and our view on the future perspectives in this research field.
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Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Animais , Proteínas Morfogenéticas Ósseas/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Fosfatos de Cálcio/química , Cerâmica/química , Cerâmica/uso terapêutico , Materiais Revestidos Biocompatíveis , Humanos , Implantes Experimentais , Propriedades de Superfície , Titânio/químicaRESUMO
Mediterranean annual forage mixtures are facing the impact of climate change, especially higher frequencies of winter-time drought. Increased mixture plasticity to climate variability is needed to mitigate this impact. However, little information exists regarding the specificities and complementarities of each forage species component to potentiate mixture resilience under drought. In this study, we identified traits with breeding potential under water scarcity through a detailed characterization of leaf and root-related parameters of 10 legume and grass species components of Mediterranean annual forage mixtures, complemented by their photosynthetic response evaluation under well-watered and water deficit conditions. This integrated approach also allowed us to identify the most resilient species to water deficit. In particular, we found that the highest canopy height and root to shoot ratio of grass components complemented well the highest aerial and root biomass and superior photosynthetic performance of the legume components. Trifolium squarrosum and Triticosecale showed the most adequate combination of traits and the best photosynthetic performance under water deficit within each species family. Although some of these traits are not commonly used in annual forage selection, they may in part explain the potential higher resilience of the grass-legume mixture under water deficit and should be considered in forage breeding.
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PURPOSE: The management of older adults with breast cancer (BC) remains controversial. The challenging assessment of aging idiosyncrasies and the scarce evidence of therapeutic guidelines can lead to undertreatment. Our goal was to measure undertreatment and assess its impact on survival. METHODS: Consecutive patients with BC aged 70 years or older were prospectively enrolled in 2014. Three frailty screening tools (G8, fTRST, and GFI) and two functional status scales (Karnofsky performance score and Eastern Cooperative Oncology Group Performance Status) were applied. Disease characteristics, treatment options, and causes of mortality were recorded during a 5-year follow-up. In addition, we defined undertreatment and correlated its survival impact with frailty. RESULTS: A total of 92 patients were included in the study. The median age was 77 (range 70-94) years. The prevalence of frailty was discordant (G8, 41.9%; fTRST, 74.2%; GFI, 32.3%). Only 47.8% of the patients had a local disease, probably due to a late diagnosis (73.9% based on self-examination). Thirty-three patients (35.6%) died, of which 15 were from BC. We found a considerably high proportion (53.3%) of undertreatment, which had a frailty-independent negative impact on the 5-year survival (hazard ratio [HR], 5.1; 95% confidence interval [CI], 2.1-12.5). Additionally, omission of surgery had a frailty-independent negative impact on overall survival (HR, 3.9; 95% CI, 1.9-7.9). CONCLUSION: BC treatment in older adults should be individualized. More importantly, assessing frailty (not to treat) is essential to be aware of the risk-benefit profile and the patient's well-informed willingness to be treated. Undertreatment in daily practice is frequent and might have a negative impact on survival, as we report.
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Syncope caused by carotid sinus syndrome due to head and neck cancer is rare. We report a case of recurrent syncope as a result of extreme bradycardia requiring pacemaker implantation. The patient began chemotherapy and radiation therapy to treat the underlying cause. When diagnosed early, a positive outcome is expected in these situations. LEARNING POINTS: The differential diagnosis of transient loss of consciousness is frequently evident at clinical examination but may prove to be a challenge.The invasion and direct compression of the carotid sinus is a rare cause of carotid sinus syndrome and presents clinically as syncope.
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Small extracellular vesicles (SEVs) offer a promising strategy for tissue regeneration, yet their short lifetime at the injured tissue limits their efficacy. Here, we show that kinetics of SEV delivery impacts tissue regeneration at tissue, cellular, and molecular levels. We show that multiple carefully timed applications of SEVs had superior regeneration than a single dose of the same total concentration of SEVs. Importantly, diabetic and non-diabetic wounds treated with a single time point dose of an injectable light-triggerable hydrogel containing SEVs demonstrated a robust increase in closure kinetics relative to wounds treated with a single or multiple doses of SEVs or platelet-derived growth factor BB, an FDA-approved wound regenerative therapy. The pro-healing activity of released SEVs was mediated at the tissue/cell level by an increase in skin neovascularization and re-epithelization and at the molecular level by an alteration in the expression of 7 miRNAs at different times during wound healing. This includes an alteration of has-miR-150-5p, identified here to be important for skin regeneration.
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Sistemas de Liberação de Medicamentos , Vesículas Extracelulares/química , Regeneração/genética , Pele/efeitos dos fármacos , Vesículas Extracelulares/transplante , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Cinética , MicroRNAs/química , Regeneração/efeitos dos fármacos , Medicina Regenerativa/métodos , Cicatrização/efeitos dos fármacosRESUMO
Essential genes are those that are critical for life. In the specific case of the mouse, they are the set of genes whose deletion means that a mouse is unable to survive after birth. As such, they are the key minimal set of genes needed for all the steps of development to produce an organism capable of life ex utero. We explored a wide range of sequence and functional features to characterise essential (lethal) and non-essential (viable) genes in mice. Experimental data curated manually identified 1301 essential genes and 3451 viable genes. Very many sequence features show highly significant differences between essential and viable mouse genes. Essential genes generally encode complex proteins, with multiple domains and many introns. These genes tend to be: long, highly expressed, old and evolutionarily conserved. These genes tend to encode ligases, transferases, phosphorylated proteins, intracellular proteins, nuclear proteins, and hubs in protein-protein interaction networks. They are involved with regulating protein-protein interactions, gene expression and metabolic processes, cell morphogenesis, cell division, cell proliferation, DNA replication, cell differentiation, DNA repair and transcription, cell differentiation and embryonic development. Viable genes tend to encode: membrane proteins or secreted proteins, and are associated with functions such as cellular communication, apoptosis, behaviour and immune response, as well as housekeeping and tissue specific functions. Viable genes are linked to transport, ion channels, signal transduction, calcium binding and lipid binding, consistent with their location in membranes and involvement with cell-cell communication. From the analysis of the composite features of essential and viable genes, we conclude that essential genes tend to be required for intracellular functions, and viable genes tend to be involved with extracellular functions and cell-cell communication. Knowledge of the features that are over-represented in essential genes allows for a deeper understanding of the functions and processes implemented during mammalian development.
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Desenvolvimento Embrionário/genética , Genes Essenciais , Animais , Expressão Gênica , CamundongosRESUMO
The presence of tumor cells in blood is predictive of short survival in several cancers and their isolation and characterization can guide toward the use of more effective treatments. These circulating tumor cells (CTC) are, however, extremely rare and require a technology that is sufficiently sensitive and specific to identify CTC against a background of billions of blood cells. Immuno-capture of cells expressing the epithelial cell adhesion molecule (EpCAM) are frequently used to enrich CTC from blood. The choice of bio conjugation strategy and antibody clone is crucial for adequate cell capture but is poorly understood. In this study, we determined the binding affinity constants and epitope binding of the EpCAM antibodies VU1D-9, HO-3, EpAb3-5, and MJ-37 by surface plasmon resonance imaging (SPRi). Glass surfaces were coated using a poly(acrylic acid) based coating and functionalized with anti-EpCAM antibodies. Binding of cells from the breast carcinoma cell line (SKBR-3) to the functionalized surfaces were compared. Although EpAb3-5 displayed the highest binding affinity HO-3 captured the highest amount of cells. Hence we report differences in the performance of the different antibodies and more importantly that the choice of antibody to capture CTC should be based on multiple assays.
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Anticorpos/metabolismo , Técnicas e Procedimentos Diagnósticos , Molécula de Adesão da Célula Epitelial , Células Neoplásicas Circulantes/metabolismo , Resinas Acrílicas/química , Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/diagnóstico , Linhagem Celular Tumoral , Técnicas e Procedimentos Diagnósticos/normas , HumanosAssuntos
Hiperplasia do Linfonodo Gigante/diagnóstico , Infecções por HIV/complicações , Herpesvirus Humano 8/isolamento & purificação , Sarcoma de Kaposi/diagnóstico , Adulto , Hiperplasia do Linfonodo Gigante/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Sarcoma de Kaposi/complicaçõesRESUMO
The microporosity of calcium phosphate (CaP) ceramics has been shown to have an essential role in osteoinduction by CaP ceramics after ectopic implantation. Here we show that it is not the microporosity but the size of surface microstructural features that is the most likely osteogenic factor. Two tricalcium phosphate (TCP) ceramics, namely TCP-S and TCP-B, were fabricated with equivalent chemistry and similar microporosity but different sizes of surface microstructural features. TCP-S has a grain size of 0.99 ± 0.20 µm and a micropore size of 0.65 ± 0.25 µm, while TCP-B displays a grain size of 3.08 ± 0.52 µm and a micropore size of 1.58 ± 0.65 µm. In vitro, both cell proliferation and osteogenic differentiation were significantly enhanced when human bone marrow stromal cells were cultured on TCP-S without any osteogenic growth factors, compared to TCP-B ceramic granules. The possible involvement of direct contact between cells and the TCP ceramic surface in osteogenic differentiation is also shown with a trans-well culture model. When the ceramic granules were implanted in paraspinal muscle of dogs for 12 weeks, abundant bone was formed in TCP-S (21 ± 10% bone in the available space), whereas no bone was formed in any of the TCP-B implants. The current in vitro and in vivo data reveal that the readily controllable cue, i.e. the size of the surface microstructure, could be sufficient to induce osteogenic differentiation of mesenchymal stem cells, ultimately leading to ectopic bone formation in calcium phosphate ceramics.
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Fosfatos de Cálcio/química , Cerâmica , Osteogênese , Adsorção , Animais , Sequência de Bases , Desenvolvimento Ósseo , Células Cultivadas , Primers do DNA , Cães , Ensaio de Imunoadsorção Enzimática , Masculino , Propriedades de Superfície , Difração de Raios XRESUMO
As unidades de alimentação e nutrição são responsáveis pelo fornecimento derefeições balanceadas e dentro de condições higiênico-sanitárias satisfatórias. O presenteestudo teve como objetivo avaliar as condições de higiene no preparo e manipulação dealimentos na Unidade de Alimentação e Nutrição do IFMA campus São Raimundo dasMangabeiras, através da aplicação de um check-list, baseado na resolução RDC 275/2002.O estudo exploratório foi realizado por meio de um guia de verificação. A avaliação por itensmostrou que o maior percentual de adequação foi verificado na matéria-prima, ingredientese embalagens e o maior percentual de inadequação foi para o item do controle de qualidadedo produto final. A referida UAN encontra-se deficiente em relação ao nível de adequaçãocom legislação. Assim, constatou-se a necessidade de se implantar as Boas Práticas defabricação (BPF).
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Boas Práticas de Fabricação , Lista de Checagem , Serviços de Alimentação/legislação & jurisprudência , Abastecimento de Alimentos/legislação & jurisprudênciaRESUMO
Circulating Tumor Cells (CTC) are rare cells originated from tumors that travel into the blood stream, extravasate to different organs of which only a small fraction will develop into metastasis. The presence of CTC enumerated with the CellSearch system is associated with a relative short survival and their continued presence after the first cycles of therapy indicates a futile therapy in patients with metastatic carcinomas. Detailed characterization of CTC holds the promise to enable the choice of the optimal therapy for the individual patients during the course of the disease. The phenotype, physical and biological properties are however not well understood making it difficult to assess the merit of recent technological advancements to improve upon the capture of CTC or to evaluate their metastatic potential. Here we will discuss the recent advances in the classification of CTC captured by the CellSearch system, the implications of their features and numbers. Latest capture platforms are reviewed and placed in the light of technology improvements needed to detect CTC. Physical properties, phenotype, viability and proliferative potential and means to assess their proliferation and metastatic capacity will be summarized and placed in the context of the latest CTC capture platforms.
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Combining technologies to engineer scaffolds that can offer physical and chemical cues to cells is an attractive approach in tissue engineering and regenerative medicine. In this study, we have fabricated polymer-ceramic hybrid scaffolds for bone regeneration by combining rapid prototyping (RP), electrospinning (ESP) and a biomimetic coating method in order to provide mechanical support and a physico-chemical environment mimicking both the organic and inorganic phases of bone extracellular matrix (ECM). Poly(ethylene oxide terephthalate)-poly(buthylene terephthalate) (PEOT/PBT) block copolymer was used to produce three dimensional scaffolds by combining 3D fiber (3DF) deposition, and ESP, and these constructs were then coated with a Ca-P layer in a simulated physiological solution. Scaffold morphology and composition were studied using scanning electron microscopy (SEM) coupled to energy dispersive X-ray analyzer (EDX) and Fourier Tranform Infrared Spectroscopy (FTIR). Bone marrow derived human mesenchymal stromal cells (hMSCs) were cultured on coated and uncoated 3DF and 3DF + ESP scaffolds for up to 21 d in basic and mineralization medium and cell attachment, proliferation, and expression of genes related to osteogenesis were assessed. Cells attached, proliferated and secreted ECM on all the scaffolds. There were no significant differences in metabolic activity among the different groups on days 7 and 21. Coated 3DF scaffolds showed a significantly higher DNA amount in basic medium at 21 d compared with the coated 3DF + ESP scaffolds, whereas in mineralization medium, the presence of coating in 3DF+ESP scaffolds led to a significant decrease in the amount of DNA. An effect of combining different scaffolding technologies and material types on expression of a number of osteogenic markers (cbfa1, BMP-2, OP, OC and ON) was observed, suggesting the potential use of this approach in bone tissue engineering.
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Osso e Ossos/citologia , Cerâmicas Modificadas Organicamente/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Regeneração Óssea , Proliferação de Células , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Microscopia Eletrônica de Varredura , Osteogênese , Medicina Regenerativa/métodos , Engenharia Tecidual/instrumentaçãoRESUMO
Calcium phosphate (CaP) based ceramics are used as bone graft substitutes in the treatment of bone defects. The physico-chemical properties of these materials determine their bioactivity, meaning that molecular and cellular responses in the body will be tuned accordingly. In a previous study, we compared two porous CaP ceramics, hydroxyapatite (HA) and ß-tricalcium phosphate (TCP), which, among other properties, differ in their degradation behaviour in vitro and in vivo, and we demonstrated that the more degradable ß-TCP induced more bone formation in a heterotopic model in sheep. This is correlated to in vitro data, where human bone marrow derived mesenchymal stromal cells (MSC) exhibited higher expression of osteogenic differentiation markers, such as osteopontin, osteocalcin and bone sialoprotein, when cultured in ß-TCP than in HA. More recently, we also showed that this effect could be mimicked in vitro by exposure of MSC to high concentrations of calcium ions (Ca(2+)). To further correlate surface physico-chemical dynamics of HA and ß-TCP ceramics with the molecular response of MSC, we followed Ca(2+) release and surface changes in time as well as cell attachment and osteogenic differentiation of MSC on these ceramics. Within 24 hours, we observed differences in cell morphology, with MSC cultured in ß-TCP displaying more pronounced attachment and spreading than cells cultured in HA. In the same time frame, ß-TCP induced expression of G-protein coupled receptor (GPCR) 5A and regulator of G-protein signaling 2, revealed by DNA microarray analysis. These genes, associated with the protein kinase A and GPCR signaling pathways, may herald the earliest response of MSC to bone-inducing ceramics.
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Materiais Biocompatíveis/farmacologia , Fosfatos de Cálcio/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Colágeno Tipo I/biossíntese , Colágeno Tipo I/genética , Humanos , Sialoproteína de Ligação à Integrina/biossíntese , Sialoproteína de Ligação à Integrina/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia Eletrônica de Varredura , Análise de Sequência com Séries de Oligonucleotídeos , Osteocalcina/biossíntese , Osteocalcina/genética , Osteogênese/genética , Osteopontina/biossíntese , Osteopontina/genética , RNA/química , RNA/genética , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The response of osteoprogenitors to calcium (Ca(2+)) is of primary interest for both normal bone homeostasis and the clinical field of bone regeneration. The latter makes use of calcium phosphate-based bone void fillers to heal bone defects, but it is currently not known how Ca(2+) released from these ceramic materials influences cells in situ. Here, we have created an in vitro environment with high extracellular Ca(2+) concentration and investigated the response of human bone marrow-derived mesenchymal stromal cells (hMSCs) to it. Ca(2+) enhanced proliferation and morphological changes in hMSCs. Moreover, the expression of osteogenic genes is highly increased. A 3-fold up-regulation of BMP-2 is observed after only 6h and pharmaceutical interference with a number of proteins involved in Ca(2+) sensing showed that not the calcium sensing receptor, but rather type L voltage-gated calcium channels are involved in mediating the signaling pathway between extracellular Ca(2+) and BMP-2 expression. MEK1/2 activity is essential for the effect of Ca(2+) and using microarray analysis, we have identified c-Fos as an early Ca(2+) response gene. We have demonstrated that hMSC osteogenesis can be induced via extracellular Ca(2+), a simple and economic way of priming hMSCs for bone tissue engineering applications.