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1.
Clin Exp Rheumatol ; 37(6): 1044-1047, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376251

RESUMO

OBJECTIVES: Several molecules are involved in the pathogenesis of new bone formation in axial spondyloarthritis (axSpA). The aim of this study was to evaluate the serum levels of BMP-2 and IL-17A in patients with axSpA and their possible correlations with radiographic damage, disease activity, and function. METHODS: AxSpA patients fulfilled the ASAS criteria and with at least New York grade 2 bilateral sacroiliitis and healthy matched controls were enrolled for this study. BASDAI, ASDAS-CRP, BASMI, BASFI and CRP were evaluated as measures of disease activity and function. Spinal damage was assessed using the mSASSS on radiographs performed within 3 months from baseline. Serum concentrations of BMP-2 and IL-17A were assessed using ELISA kit. RESULTS: Sixty patients and 30 healthy subjects satisfying the inclusion criteria were enrolled. In our axSpA group, serum BMP-2 levels [median (25th-75th percentile) of 589.2 (430.24-1017.1) pg/ml] did not statistically differ from controls [518.34 (450.2-1028.2) pg/ml]. However, significant correlations were found between serum BMP-2 levels and radiographic damage assessed by mSASSS, and BMP-2 levels were found to be higher in patients with grade 4 sacroiliitis when compared to patients with lower grade of sacroiliitis. Of note, serum BMP-2 levels significantly inversely correlate with IL-17A levels and CRP, and were found to be lower in patients with higher disease activity. CONCLUSIONS: The results of our study may confirm a possible role of BMP-2 in the pathogenesis of new bone formation in axSpA patients. Furthermore, a link between inflammation and BMP-2 was found.


Assuntos
Proteína Morfogenética Óssea 2/sangue , Interleucina-17/sangue , Osteogênese , Espondilartrite/sangue , Estudos de Casos e Controles , Estudos Transversais , Humanos , Índice de Gravidade de Doença
2.
J Pak Med Assoc ; 69(6): 913-914, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31201406

RESUMO

A number of different serum biomarkers are currently being evaluated for their potential use as diagnostic and prognostic biomarkers in Glioblastoma Multiforme. Amongst these, a vast number of different microRNAs have been studied, that are up-regulated or downregulated in relation to Glioblastoma Multiforme. Different studies have found numerous associations of these different microRNAs with recurrence, Karnofsky Performance Score, Progression Free Survival and Overall Survival. Other than microRNAs, serum Glial Fibrillary Acid Protein, cytokines and YLK-40, as well as a number of other candidate serum biomarkers are being studied.More studies, with larger sample sizes are required before these serum biomarkers can be routinely, and reliably used in clinical practice. Use of serum biomarkers can provide a non-invasive means for diagnosing and monitoring disease.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Citocinas/sangue , Glioblastoma/sangue , MicroRNAs/sangue , Proteína Morfogenética Óssea 2/sangue , Neoplasias Encefálicas/mortalidade , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína Glial Fibrilar Ácida/sangue , Glioblastoma/mortalidade , Humanos , Avaliação de Estado de Karnofsky , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Intervalo Livre de Progressão , Taxa de Sobrevida
3.
J Ethnopharmacol ; 241: 111977, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31136804

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Oxidative damage to osteoblasts was a key factor in the development of osteoporosis. Er-Xian Decotion (EXD) is widely used in China for the treatment of osteoporosis, which has a variety of antioxidant active ingredients. EXD may be an important source of protection against oxidative damage in osteoblasts, but the anti-osteoporotic active components of EXD is currently unclear. AIM OF THE STUDY: This work established an effective and reliable drug screening method to find main active ingredients in EXD (M-EXD) that can protect osteoblasts against oxidative stress and achieve anti-osteoporosis effects. MATERIALS AND METHODS: H2O2-induced osteoblast cell fishing with UHPLC-QTOF/MS was firstly used to discover the potential active components from EXD. Afterword, the EXD compound-osteoporosis target network was constructed using network pharmacology, thus potentially anti-osteoporosis ingredients were founded, and their combination were defined as the M-EXD. Finally, pharmacology effects of M-EXD was evaluated by ovariectomized rats, prednisolone induced-zebrafish and H2O2-induced osteoblasts. RESULTS: 40 candidate active ingredients in EXD were initially screened out via pathological cell fishing. According to network pharmacology result, M-EXD consisted of 13 ingredients since they had a close relationship with 65 osteoporosis-related targets. Pharmacological evaluation showed that M-EXD significantly ameliorated oxidative stress in H2O2-induced osteoblast model, evidently reversed the activity of ALP, ROS, GSH-px, NO and MDA compared with the model group. M-EXD showed better anti-oxidative activities than individual ingredients, presenting obvious synergetic effects. In osteoporosis rat and zebrafish models, M-EXD also demonstrated good anti-osteoporotic properties by mitigating the osteoporosis bone loss and increasing serum bone morphogenetic protein 2, and reversing osteocalcin expression in bone tissue. It significantly ameliorated oxidative stress in the in-vivo models. Moreover, M-EXD and EXD showed similar anti-osteoporotic and anti-oxidative properties, while the rest components of EXD had no satisfactory anti-osteoporotic efficacy. CONCLUSIONS: Our work successfully identified the main active components in EXD, which could represent the efficacy of EXD on treating osteoporosis, and meanwhile, it also provided an effective strategy to investigate active ingredients from natural medicines, which might be helpful for drug development and application.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Animais , Proteína Morfogenética Óssea 2/sangue , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Peixe-Zebra
4.
Med Sci Monit ; 24: 4363-4371, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29938690

RESUMO

BACKGROUND To investigate the effect of the BMP/Smad signaling pathway on fracture healing and osteogenic ability in senile osteoporotic fracture on humans and rats. MATERIAL AND METHODS Sixty-two patients and well-matched normal controls were enrolled for clinical observation. A rat model of senile osteoporotic fracture was established. Serum BMP2 and Smad4 levels, as well as alkaline phosphatase (ALP) activity, were detected by ELISA. Fracture healing was observed by X-ray radiography and bone formation was analyzed by micro-CT. RESULTS Serum BMP2 and Smad4 levels in patients with senile osteoporotic fracture were significantly lower than those in normal controls (all P<0.01). BMP2 was highly positively correlated with Smad4 in patients with senile osteoporotic fracture (r=0.738). Compared with patients with low serum BMP2 and Smad4 levels, visual analog scale scores decreased, bone mineral density (BMD) increased, and duration of fracture healing was shortened in patients with high levels (all P<0.05). Compared with the Model group, serum BMP2 and Smad4 levels increased, fracture healing was improved, BMD, trabecular bone volume (TBV), tissue volume (TV), bone volume fraction (BV/TV), mean trabecular thickness (Tb. Th), and mean number of trabecular bone (Tb. N) were increased, and ALP activity increased in the BMP2 overexpression group (all P<0.05), while each index in the NC group showed no statistical difference relative to rats in the Model group (all P>0.05). CONCLUSIONS BMP2 overexpression can promote fracture healing and osteogenic ability in senile osteoporotic fractures through activating the BMP/Smad signaling pathway.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Consolidação da Fratura , Osteogênese , Fraturas por Osteoporose/metabolismo , Transdução de Sinais , Proteína Smad4/metabolismo , Idoso , Fosfatase Alcalina/sangue , Animais , Densidade Óssea , Proteína Morfogenética Óssea 2/sangue , Calo Ósseo/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/fisiopatologia , Ratos , Proteína Smad4/sangue
5.
Biomed Res Int ; 2018: 8371604, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850574

RESUMO

Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP) signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA), and matrix Gla protein (MGP) in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor) rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (r = 0.929; P < 0.01) and serum BMP-4 (r = 0.702; P < 0.01) levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.


Assuntos
Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 4/genética , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/genética , Regulação para Cima/genética , Calcificação Vascular/complicações , Calcificação Vascular/genética , Animais , Aorta/metabolismo , Aorta/patologia , Peso Corporal , Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/sangue , Proteína Morfogenética Óssea 4/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio , Ensaio de Imunoadsorção Enzimática , Proteínas da Matriz Extracelular , Rim/patologia , Rim/fisiopatologia , Masculino , Tamanho do Órgão , Proteinúria/complicações , Proteinúria/genética , Ratos Sprague-Dawley , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Calcificação Vascular/fisiopatologia , Calcificação Vascular/urina
6.
J Neuroimmunol ; 310: 120-128, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28778435

RESUMO

Blockage of bone morphogenetic protein (BMP) signaling is required for differentiation of neurons and oligodendrocytes from neural stem cells (NSCs). Sera of untreated relapsing-remitting multiple sclerosis (RR-MS) patients expressed significantly higher levels of BMP-2 compared to sera of healthy controls. BMP-2 levels correlated with BMP-4 and -5 levels only in sera of untreated MS patients. Furthermore, sera of untreated patients inhibited the neuronal differentiation of RA-treated P19 cells, which was associated with induction of phospho-SMAD signaling pathway. These results suggest that BMP-2 sera levels may play a role in the failure of remyelination and neuro-regeneration in RR-MS.


Assuntos
Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 4/sangue , Proteína Morfogenética Óssea 5/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/patologia , Células-Tronco Neurais/metabolismo , Adolescente , Adulto , Citocinas/sangue , Avaliação da Deficiência , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interferon beta/farmacologia , Interferon beta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Células-Tronco Neurais/efeitos dos fármacos , Oligodendroglia/metabolismo , Transdução de Sinais/fisiologia , Proteínas Smad/metabolismo , Estatística como Assunto , Adulto Jovem
7.
J Biol Chem ; 292(37): 15352-15368, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28747434

RESUMO

Bone morphogenetic proteins (BMPs) regulate diverse cellular responses during embryogenesis and in adulthood including cell differentiation, proliferation, and death in various tissues. In the adult pituitary, BMPs participate in the control of hormone secretion and cell proliferation, suggesting a potential endocrine/paracrine role for BMPs, but some of the mechanisms are unclear. Here, using a bioactivity test based on embryonic cells (C3H10T1/2) transfected with a BMP-responsive element, we sought to determine whether pituitary cells secrete BMPs or BMP antagonists. Interestingly, we found that pituitary-conditioned medium contains a factor that inhibits action of BMP-2 and -4. Combining surface plasmon resonance and high-resolution mass spectrometry helped pinpoint this factor as thrombospondin-1 (TSP-1). Surface plasmon resonance and co-immunoprecipitation confirmed that recombinant human TSP-1 can bind BMP-2 and -4 and antagonize their effects on C3H10T1/2 cells. Moreover, TSP-1 inhibited the action of serum BMPs. We also report that the von Willebrand type C domain of TSP-1 is likely responsible for this BMP-2/4-binding activity, an assertion based on sequence similarity that TSP-1 shares with the von Willebrand type C domain of Crossveinless 2 (CV-2), a BMP antagonist and member of the chordin family. In summary, we identified for the first time TSP-1 as a BMP-2/-4 antagonist and presented a structural basis for the physical interaction between TSP-1 and BMP-4. We propose that TSP-1 could regulate bioavailability of BMPs, either produced locally or reaching the pituitary via blood circulation. In conclusion, our findings provide new insights into the involvement of TSP-1 in the BMP-2/-4 mechanisms of action.


Assuntos
Proteína Morfogenética Óssea 2/antagonistas & inibidores , Proteína Morfogenética Óssea 4/antagonistas & inibidores , Modelos Moleculares , Hipófise/metabolismo , Elementos de Resposta , Trombospondina 1/metabolismo , Animais , Animais Endogâmicos , Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/sangue , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Linhagem Celular , Células Cultivadas , Biologia Computacional , Feminino , Genes Reporter , Humanos , Camundongos , Hipófise/citologia , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Carneiro Doméstico , Trombospondina 1/química , Trombospondina 1/isolamento & purificação
8.
Clin Chim Acta ; 471: 150-153, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28558956

RESUMO

OBJECTIVE: This study aimed to assess the association between plasma bone morphogenetic protein-2 (BMP-2) level and in-stent restenosis in patients with coronary artery disease. METHODS: A total of 96 patients who underwent percutaneous coronary intervention (PCI) and were followed up after PCI were enrolled in this study. 47 patients diagnosed with in-stent restenosis (ISR) were recruited to ISR group and 49 patients without ISR were recruited to Control group according to the results of coronary angiography (CAG). Baseline characteristic data were collected, and plasma BMP-2 level was evaluated. The results were analyzed using logistic regression. RESULTS: There were 47 patients in the ISR group and 49 patients in the Control group. Plasma levels of BMP-2 were higher in the ISR group than in the non-ISR group [20.96 (18.44, 27.05) pg/ml vs. 29.53 (25.03, 34.07) pg/ml, P<0.01]. Furthermore, the ISR group had significantly longer stent lengths and lower stent diameters than the Control group (P<0.01 and P<0.01, respectively). In multivariate analysis, BMP-2 level, diabetes, stent length and stent diameter were independently associated with ISR [odds ratio (OR)=1.11, 95% confidence interval (CI)=1.03-1.18, P<0.01; OR=4.75, 95% CI=(1.44-15.61), P=0.01; OR=1.06, 95% CI=(1.02-1.11), P<0.01; and OR=0.15, 95% CI=(0.02-0.95), P=0.04, respectively]. CONCLUSIONS: Increased BMP-2 levels were independently associated with ISR in patients with coronary artery disease. Plasma BMP-2 may be useful in predicting ISR.


Assuntos
Proteína Morfogenética Óssea 2/sangue , Doença da Artéria Coronariana/sangue , Reestenose Coronária/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea
9.
J Nippon Med Sch ; 84(1): 12-18, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331138

RESUMO

BACKGROUND: The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-ß1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. MATERIALS AND METHODS: We performed a comprehensive analysis of plasma TGF-ß1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-ß1 and BMP-2 were measured at each time point using a solid-phase ELISA. RESULTS: TGF-ß1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-ß1 was found at 3-week. In normal union group, TGF-ß1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-ß1 or BMP-2 level was not significantly different between normal union and nonunion groups. CONCLUSION: The expression levels of TGF-ß1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.


Assuntos
Proteína Morfogenética Óssea 2/sangue , Consolidação da Fratura/genética , Consolidação da Fratura/fisiologia , Fraturas Ósseas/genética , Fraturas Ósseas/fisiopatologia , Fraturas Mal-Unidas/diagnóstico , Fraturas Mal-Unidas/genética , Expressão Gênica , Fator de Crescimento Transformador beta1/sangue , Adulto , Biomarcadores/sangue , Proteína Morfogenética Óssea 2/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Fator de Crescimento Transformador beta1/fisiologia , Adulto Jovem
10.
Gene ; 588(2): 163-72, 2016 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-27196063

RESUMO

CONTEXT: Few potential candidate genes coding for type I and II receptors of transforming growth factor beta signaling pathway and the serotonin transporter have been associated with pulmonary hypertension (PH). The latter being a phenotype for high altitude pulmonary edema (HAPE), these genes are hypothesized to be crucial markers to investigate under the hypobaric hypoxic environment of high altitude. AIMS: We hence aimed to investigate bone-morphogenetic protein-2 (BMP2), bone morphogenetic protein receptor type-II (BMPR-2), activin receptor-like kinase-1 (ALK-1), serotonin transporter (5-HTT) and serotonin (5-HT) for their contribution, individually/epistatically, to clinical endpoints by altering downstream signaling molecules. METHODS AND MATERIALS: In a case-control design, interactions between/among polymorphisms of BMPR-2, ALK-1 and 5-HTT were screened in 200 HAPE-patients (HAPE-p) and 200 HAPE-free sojourners (HAPE-f). Plasma biomarker BMP-2 and 5-HT were estimated. The relative gene expression was also witnessed in 20 humans/10 rats followed by correlation analyses. RESULTS: The genotype/allele models revealed the prevalence of BMPR-2 rs6717924A-rs4303700A-rs1048829A; ALK-1 rs11169953T-rs3759178C-rs706816C and 5-HTT rs6354C in HAPE (P≤0.05). Multifactor dimensionality reduction for interactions among genes revealed a 4-locus model of BMPR-2 rs6717924G/A; ALK-1 rs11169953C/T-rs706816T/C and 5-HTT rs6354A/C as the best disease predicting (P≤0.001); whereas HapEvolution analysis confirmed the alleles rs6717924A, rs4303700A and rs6354C as the best interacting (P≤0.01). Plasma levels of BMP-2 and 5-HT were elevated in HAPE (P≤0.0001). The expression of BMP-2, ALK-1, 5-HT, 5-HTT was elevated and of BMPR-2 decreased in humans and rats (P≤0.05). The risk alleles BMPR-2 rs6717924A-rs4303700G-rs1048829A; ALK-1 rs11169953T-rs706816C and 5-HTT rs6354C correlated inversely with arterial oxygen saturation (SaO2) and positively with mean arterial pressure (MAP), BMP-2 and 5-HT in HAPE. Likewise, haplotypes BMPR-2 GGGCGAAAA, AAATAGGGA and ALK-1 CCTCAAAG, CCTTAAAG correlated with clinical markers and biomarkers (P≤0.01). BMP-2 and 5-HT correlated positively with MAP and negatively with SaO2 (P≤0.01). CONCLUSIONS: The genetic-interactions among BMPR-2, ALK-1, and 5-HTT polymorphisms, elevated BMP-2 and 5-HT levels and differential gene expression substantiated the strong genetic contribution in HAPE pathophysiology.


Assuntos
Receptores de Activinas Tipo II/genética , Doença da Altitude/genética , Proteína Morfogenética Óssea 2/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Hipertensão Pulmonar/genética , Hipóxia/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Receptores de Activinas Tipo II/metabolismo , Alelos , Altitude , Doença da Altitude/metabolismo , Doença da Altitude/fisiopatologia , Animais , Pressão Arterial , Proteína Morfogenética Óssea 2/sangue , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Estudos de Casos e Controles , Epistasia Genética , Haplótipos , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Modelos Genéticos , Redução Dimensional com Múltiplos Fatores , Polimorfismo Genético , Ratos , Ratos Wistar , Serotonina/sangue , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Transdução de Sinais
11.
Cardiovasc Diabetol ; 14: 64, 2015 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-26003174

RESUMO

BACKGROUND: Although Bone morphogenetic protein-2 (BMP-2) is a known mediator of bone regeneration and vascular calcification, to date no study has investigated the relationship between BMP-2 and type 2 diabetes mellitus (T2DM) and its possible role in coronary artery disease (CAD). The purpose of this study is to evaluate the relationship of BMP-2 with atherosclerosis and calcification in patients with T2DM. METHODS: 124 subjects were enrolled in this study: 29 patients with T2DM and CAD; 26 patients with T2DM and without CAD; 36 patients with CAD and without T2DMand 34 without T2DM or CAD (control group). Severity of coronary lesions was assessed using coronary angiography and intravascular ultrasound (IVUS). Plasma BMP-2 levels were quantified using a commercially available ELISA kit. RESULTS: Compared to the control group, the mean plasma BMP-2 level was significantly higher in T2DM patients with or without CAD (20.1 ± 1.7 or 19.3 ± 1.5 pg/ml, vs 17.2 ± 3.3 pg/ml, P < 0.001). In a multivariable linear regression analysis, both T2DM and CAD were significantly and positively associated with BMP-2 (Estimate, 0.249; standard error (SE), 0.063; p <0.0001; Estimate, 0.400; SE, 0.06; p < 0.0001). Plasma BMP-2 was also strongly correlated with glycosylated hemoglobin A1c (HbA1c) (Spearman ρ = -0.31; p = 0.0005). SYNTAX score was also significantly associated with BMP-2 (Spearman ρ = 0.46; p = 0.0002). Using the results from IVUS, plasma BMP-2 levels were shown to positively correlate with plaque burden (Spearman ρ = 0.38, P = 0.002) and plaque calcification (Spearman ρ =0.44, P = 0.0003) and to negatively correlate with lumen volume (Spearman ρ =0.31, P = 0.01). CONCLUSIONS: Our study demonstrates that patients with T2DM had higher circulating levels of BMP-2 than normal controls. Plasma BMP-2 levels correlated positively with plaque burden and calcification in patients with T2DM.


Assuntos
Aterosclerose/sangue , Proteína Morfogenética Óssea 2/sangue , Doença da Artéria Coronariana/sangue , Diabetes Mellitus Tipo 2/sangue , Calcificação Vascular/sangue , Idoso , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Ultrassonografia de Intervenção , Calcificação Vascular/complicações , Calcificação Vascular/diagnóstico por imagem
12.
Med Sci Monit ; 21: 363-70, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25644704

RESUMO

BACKGROUND: This study aimed to investigate the bone morphogenetic protein-2 (BMP-2) levels in serum and synovial fluid (SF) of patients with primary knee osteoarthritis (OA) and to exam its correlation with radiographic and symptomatic severity of the disease. MATERIAL/METHODS: A total of 37 knee OA patients and 20 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to the Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed in anteroposterior knee radiography. Symptomatic severity of the disease was evaluated according to the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. BMP-2 levels in serum and SF were determined using enzyme-linked immunosorbent assay. RESULTS: Serum BMP-2 level in patients with knee OA was higher than that in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated BMP-2 levels in the serum and SF compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had significant higher SF levels of BMP-2 than those with KL grade 2. BMP-2 levels in the serum and SF of knee OA patients were both positively correlated with KL grades and WOMAC scores. CONCLUSIONS: BMP2 levels in serum and SF were closely related to the radiographic and symptomatic severity of knee OA and may serve as an alternative biochemical parameter to determine disease severity of primary knee OA.


Assuntos
Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 2/química , Osteoartrite do Joelho/sangue , Líquido Sinovial/química , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Joelho/patologia , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Radiografia
13.
Mol Med Rep ; 11(3): 2199-206, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25394514

RESUMO

The present study aimed to identify the characteristics and cross­talk between transforming growth factor ß1 (TGF­ß1) and calcium ions in nephrolithiasis patients with idiopathic hypercalciuria (IH) in order to elucidate the potential mechanisms underlying changes in cell phenotype induced by bone­associated factors and their influence on renal nephrolithiasis formation. Blood samples from a total of 29 nephrolithiasis patients with IH, 29 renal stone patients without IH and 29 healthy age­matched normal controls were subjected to quantification of peripheral serum TGF­ß1, osteopontin (OPN) and bone morphogenetic protein 2 (BMP2) using ELISA. This was followed by detection of BMP2, OPN and 1,25­dihydroxyvitamin D3 receptor (VDR) mRNA and protein levels in primary renal epithelial cells (PRECs) of IH and HK­2 human proximal tubular cell lines (control) using reverse transcription quantitative polymerase chain reaction (RT­qPCR) and western blot analyses. The mRNA expression levels of BMP2, OPN and VDR in PRECs and HK­2 were evaluated following stimulation with various concentrations of TGF­ß1 (0.5, 2.0 and 5.0 ng/ml), Ca2+ (0.5, 1.5 and 2.5 mM) or TGF­ß1 and Ca2+ combined using RT­qPCR, respectively. TGF­ß1, BMP2 and OPN expression levels in patients with IH were all significantly higher than those in the control group. The mRNA and protein expression levels of BMP2 and VDR were significantly higher in PRECs than those in HK­2 cells. Following incubation with TGF­ß1 and/or Ca2+, the mRNA expression levels of BMP2, OPN and VDR in PRECs increased in a dose­dependent manner; however, no significant differences were observed in HK­2 cells with increasing TGF­ß1 dosage. Co­incubation with TGF­ß1 and Ca2+ in PRECs and HK­2 cell lines resulted in similar effects and the expression of BMP2, OPN and VDR mRNA increased in a time­dependent manner. In conclusion, the results of the present study demonstrated that TGF­ß1 regulated the expression of BMP2, OPN and VDR in PRECs, but not in HK­2 cells. Co­incubation with TGF­ß1 and Ca2+ significantly increased the expression levels of bone­associated factors in PRECs and HK­2 cells, which suggested that this process may be partially responsible for the pathogenesis of calcium stone development, and also associated with bone formation and the TGF­ß1­induced epithelial to mesenchymal transition.


Assuntos
Cálcio/metabolismo , Transdiferenciação Celular , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Hipercalciúria/metabolismo , Rim/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Transdiferenciação Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Hipercalciúria/genética , Rim/citologia , Masculino , Pessoa de Meia-Idade , Nefrolitíase/genética , Nefrolitíase/metabolismo , Osteopontina/sangue , Osteopontina/metabolismo , Fenótipo , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/farmacologia , Adulto Jovem
14.
Acta Medica (Hradec Kralove) ; 57(2): 56-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25257151

RESUMO

INTRODUCTION: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. AIM: The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. METHODS: Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. RESULTS: In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). CONCLUSION: Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.


Assuntos
Proteína Morfogenética Óssea 2/sangue , Espondilite Anquilosante/sangue , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Proteína C-Reativa/metabolismo , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Chin J Integr Med ; 20(8): 600-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25087604

RESUMO

OBJECTIVE: To investigate the effect of Ermiao Recipe (, EMR) with medicinal guide Angelicae Pubescentis Radix (APR) on the homing of bone marrow stem cells (BMSCs) to focal zone in osteoarthritis (OA) rats. METHODS: Forty-eight Sprague-Dawley rats were randomly assigned to the sham-operated, model, EMR, and EMR plus APR groups (12 rats in each group). The OA rat model was induced by anterior cruciate ligament transection and medial meniscus resection. All rats were injected with recombinant human granulocyte colonystimulating factor [rhG-CSF, 30 µg/(kg·d) for continuous 7 days], and rats in the EMR and EMR plus APR groups were treated with EMR or EMR plus APR at 1.6 or 1.9 g/(kg·d) for 3 or 6 weeks, respectively. Cartilage histopathologic changes were observed by hematoxylin and eosin staining. Chondrocytes apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Interleukin-1ß (IL-1 ß), tumor necrosis factor α (TNF-α), bone morphogenetic protein 2 (BMP-2), and transforming growth factor beta-1 (TGF-ß1) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay assay. Matrix metalloproteinase (MMP)-13, tissue inhibitors of metalloproteinase (TIMP)-1, bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemistry assay. RESULTS: EMR and EMR plus APR significantly inhibited articular cartilage damage and synovium inflammation in OA rats at 3 or 6 weeks of treatment, the most obvious changes in these parameters were found in the EMR plus APR group. At 6 weeks, compared with EMR treatment, EMR plus APR remarkably inhibited chondrocytes apoptosis and the release of IL-1ß and TNF-α, obviously decreased MMP-13 expression, and significantly increased expressions of proteoglycan, collagen, type II collagen and TIMP-1, serum levels of BMP-2 and TGF-ß1 as well as expressions of BrdU, CD34 and SDF-1 in cartilage articular (P<0.01 or P<0.05). CONCLUSION: The medicinal guide APR improved the therapeutic effects of EMR on OA rats by promoting directional homing of BMSCs to focal zone.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Cartilagem Articular/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Proteína Morfogenética Óssea 2/sangue , Bromodesoxiuridina/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/enzimologia , Quimiocina CXCL12/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Medicamentos de Ervas Chinesas/farmacologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Interleucina-1beta/sangue , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/sangue , Osteoartrite/sangue , Osteoartrite/patologia , Ratos Sprague-Dawley , Membrana Sinovial/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta1/sangue , Fator de Necrose Tumoral alfa/sangue
16.
Drug Chem Toxicol ; 37(1): 40-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23841455

RESUMO

Escherichia coli-derived recombinant human (rh)BMP-2 (E.BMP-2) can be used as a bone graft substitute because to its high osteoinductivity, but its toxicity is not well understood. Thus, we report on the toxicity of E.BMP-2 in Sprague-Dawley rats under the condition of repetitive injection for 2 weeks. Randomly selected 10 male and female rats were administered with E.BMP-2 at a dose of 0.05, 0.18 or 0.5 mg/kg as an experimental group. A control group with another 10 rats was given E.BMP-2 carrier. Both E.BMP-2 and E.BMP-2 carrier were administered through intravenous injection for 2 weeks. For toxicokinetics study, 3 male and female rats were randomly selected from each group. During the observation period, general symptom, weight and food intakes were monitored, and ophthalmic and urine tests were performed as well. After the observation period, all animals were subjected to blood test, biochemical analysis and organ-weight measurement. During autopsy, visual inspections and histopathological examinations were done. Toxicokinetics study confirmed systemic exposure of the test material. No death or abnormal clinical sign was found during the injection period. Toxicity changes induced by the injection were not detected in autopsy or the tests for weight, food intakes, ophthalmology, hematology and serum biochemistry. The female groups administered with 0.18 and 0.5 mg/kg (the female 0.18-mg/kg group and the female 0.5-mg/kg group) showed absolute and relative weight loss in ovaries and reduced corpora lutea. It was the expected pharmacologic activity, rather than toxicity. The histopathological test revealed cartilage formation and increased fibroblast around the tail vein, but these were thought to be the result of osteoinductivity of the test material. In the male group with 0.5 mg/kg of E.BMP-2 (the male 0.5-mg/kg group), local appearance of multinucleated cells in lung parenchyma was observed, but it was considered as the natural reaction to remove E.BMP-2, which is a recombinant protein. In toxicokinetics study, systemic exposure (area under the serum concentration-time curve and maximum observed serum concentration) increased as the injection dose was increased in both male and female rats, and no clear difference was noticed between the sexes. Blood drug content did not change during the injection period, but the half-life was shortened as the injection dose was increased. Under the condition of this study, the no observed adverse effects level of E.BMP-2 was over 0.5 mg/kg in both male and female rats.


Assuntos
Proteína Morfogenética Óssea 2/farmacocinética , Proteína Morfogenética Óssea 2/toxicidade , Escherichia coli/química , Fator de Crescimento Transformador beta/farmacocinética , Fator de Crescimento Transformador beta/toxicidade , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Proteína Morfogenética Óssea 2/administração & dosagem , Proteína Morfogenética Óssea 2/sangue , Corpo Lúteo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Injeções Intravenosas , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/toxicidade , Estatísticas não Paramétricas , Testes de Toxicidade , Fator de Crescimento Transformador beta/administração & dosagem , Fator de Crescimento Transformador beta/sangue , Urinálise
17.
Asian Pac J Cancer Prev ; 14(9): 5293-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24175816

RESUMO

PURPOSE: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer. This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patients with non-small-cell lung cancer (NSCLC). METHODS: Blood samples from 84 patients with advanced NSCLC and 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles of chemotherapy using a commercially available ELISA kit. RESULTS: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observed between pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases (P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after two cycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stage were significantly correlated with poor prognosis. CONCLUSION: Thes erum BMP-2 level is positively correlated with clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor for prognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.


Assuntos
Adenocarcinoma/mortalidade , Biomarcadores Tumorais/sangue , Proteína Morfogenética Óssea 2/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/sangue , Adenocarcinoma/secundário , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Curva ROC , Taxa de Sobrevida
18.
Epilepsy Res ; 107(1-2): 56-60, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24035343

RESUMO

OBJECTIVE: To determine the effect of levetiracetam (LEV) Lon bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomised (ORX) rat model. METHOD: 16 orchidectomised Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LEV for 12 weeks. BMD was measured by dual energy X-ray absorptiometry at the whole body, lumbar spine and femur. Bone marker concentrations were examined of osteoprotegerin (OPG) and insulin-like growth factor 1 (IGF-1) in serum, and amino-terminal propeptide of procollagen type I (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (ALPL), and bone morphogenetic protein 2 (BMP-2) in bone homogenate. The femurs were used for biomechanical testing. RESULTS: Compared to the control group we found lower fat mass, lower BMD in the area of the left femur, lower BMC in both femurs, a reduced concentration of OPG, and an increased concentration of CTX-I of borderline statistical significance (p=0.0661). Biomechanical parameters did not differ between groups. CONCLUSIONS: Significant loss of BMD or BMC was seen at the left and right femur area in the LEV group. Administration of LEV in the ORX-rat model significantly decreased levels of OPG (marker of bone formation) in serum and increased levels of CTX-I (marker of bone resorption) in bone homogenate, but results in this study did not reveal any change in biomechanical bone strength. Administration of LEV in the ORX-rat model may reduce adipose tissue. Further studies in animals and humans will be needed to confirm these findings.


Assuntos
Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Piracetam/análogos & derivados , Fosfatase Alcalina/sangue , Animais , Biomarcadores/sangue , Proteína Morfogenética Óssea 2/sangue , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Levetiracetam , Masculino , Osteoprotegerina/sangue , Piracetam/farmacologia , Ratos , Ratos Wistar
19.
J Orthop Res ; 31(1): 44-52, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22778059

RESUMO

To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients ≥8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme-linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p < 0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Osteoartrite do Quadril/sangue , Osteoartrite do Quadril/diagnóstico , Transtornos da Articulação Temporomandibular/sangue , Transtornos da Articulação Temporomandibular/diagnóstico , alfa-2-Glicoproteína-HS/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição , Artroplastia de Quadril , Biomarcadores/sangue , Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 4/sangue , Proteína Morfogenética Óssea 7/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/cirurgia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Índice de Gravidade de Doença , Transtornos da Articulação Temporomandibular/cirurgia , Adulto Jovem
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