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  • Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density. 24789909

    Patient bone mineral density (BMD) predicts the likelihood of osteoporotic fracture. While substantial progress has been made toward elucidating the genetic determinants of BMD, our understanding of the factors involved remains incomplete. Here, using a systems genetics approach in the mouse, we predicted that bicaudal C homolog 1 (Bicc1), which encodes an RNA-binding protein, is responsible for a BMD quantitative trait locus (QTL) located on murine chromosome 10. Consistent with this prediction, mice heterozygous for a null allele of Bicc1 had low BMD. We used a coexpression network-based approach to determine how Bicc1 influences BMD. Based on this analysis, we inferred that Bicc1 was involved in osteoblast differentiation and that polycystic kidney disease 2 (Pkd2) was a downstream target of Bicc1. Knock down of Bicc1 and Pkd2 impaired osteoblastogenesis, and Bicc1 deficiency-dependent osteoblast defects were rescued by Pkd2 overexpression. Last, in 2 human BMD genome-wide association (GWAS) meta-analyses, we identified SNPs in BICC1 and PKD2 that were associated with BMD. These results, in both mice and humans, identify Bicc1 as a genetic determinant of osteoblastogenesis and BMD and suggest that it does so by regulating Pkd2 transcript levels.
    Tipo de documento:
    Referencia
    Referencia del producto:
    04-1116
  • Fracture resistance and histological findings of immature teeth treated with mineral trioxide aggregate. 18410392

    The objective of the present study was to test the hypothesis that the fracture strength of calcium hydroxide and mineral trioxide aggregate (MTA)-filled immature teeth decreased over time. Immature mandibular incisors from sheep were extracted and the pulps were extirpated using an apical approach with a barbed broach, and the teeth were divided into three experimental groups. Group 1: untreated teeth. Group 2: the root canals were filled with calcium hydroxide paste. Group 3: the root canals were filled with MTA. All specimens were kept in saline with 1% antibiotics at 4 degrees C for certain periods of time: 2 weeks, 2 months, and 1 year. Then they were tested for fracture strength in an Instron testing machine. The results were subjected to statistical analysis by the Tukey-Kramer tests. A P-value (0.05) was considered statistically significant. One tooth from each group was selected randomly for a histological study, examining matrix metalloproteinases (MMP2 and MMP14) and tissue inhibitor of metalloproteinase (TIMP). The results showed the mean fracture strengths decreased over time for all the three groups. Although the untreated teeth showed the highest value (45.5 MPa) at 2 weeks, the fracture strengths decreased significantly after 2 months (P 0.05). On the other hand, the teeth treated with calcium hydroxide or MTA decreased, but not significantly over time (P 0.05). For the MTA-treated teeth, the fracture strengths were not found significantly different from the untreated or calcium hydroxide-treated teeth at 2 weeks or 2 months (P 0.05). However, the strength was significantly higher in the MTA group compared with the other two groups after 1 year (P 0.05). Immunofluorescence images revealed expression of collagen type 1, MMP-2 and MMP-14 in both untreated and endodontically treated teeth. However, TIMP-2 was only observed in the MTA-treated teeth. In conclusion, the teeth with root treatment with MTA showed the highest fracture resistance at 1 year (P 0.05). An explanation could be that MTA induced the expression of TIMP-2 in the dentin matrix and thereby possibly prevented destruction of the collagen matrix.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB3310
    Nombre del producto:
    Anti-TIMP-2 Antibody, clone 67-4H11
  • Loss of insulin receptor in osteoprogenitor cells impairs structural strength of bone. 24963495

    Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10-12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB374
    Nombre del producto:
    Anti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5
  • Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. 17159017

    BACKGROUND: Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exercise (EX) is unknown. We tested the hypothesis that EX-induced weight loss is associated with less bone loss compared with CR-induced weight loss. METHODS: Forty-eight adults (30 women; 18 men; mean +/- SD age, 57 +/- 3 years; and mean +/- SD body mass index, 27 +/- 2 kg/m2) were randomized to 1 of 3 groups for 1 year: CR group (n = 19), regular EX group (n = 19), or a healthy lifestyle (HL) control group (n = 10). Primary outcome measure was change in hip and spine bone mineral density (BMD). Secondary outcomes were bone markers and hormones. RESULTS: Body weight decreased similarly in the CR and EX groups (10.7% +/- 6.3% [-8.2 +/- 4.8 kg] vs 8.4% +/- 6.3% [-6.7 +/- 5.6 kg]; P = .21), whereas weight did not change in the HL group (-1.2% +/- 2.5% [-0.9 +/- 2.0 kg]). Compared with the HL group, the CR group had decreases in BMD at the total hip (-2.2% +/- 3.1% vs 1.2% +/- 2.1%; P = .02) and intertrochanter (-2.1% +/- 3.4% vs 1.7 +/- 2.8%; P = .03). The CR group had a decrease in spine BMD (-2.2% +/- 3.3%; P = .009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R = 0.61; P = .007) but not in the EX group. Bone turnover increased in both CR and EX groups. CONCLUSIONS: CR-induced weight loss, but not EX-induced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone.
    Tipo de documento:
    Referencia
    Referencia del producto:
    HL-81K
    Nombre del producto:
    Human Leptin RIA
  • The influence of ghrelin, adiponectin, and leptin on bone mineral density in healthy postmenopausal women. 18979162

    The association of body fat mass (FM) with bone mineral mass (BMC) and bone mineral density (BMD) has been attributed to a mechanical load exerted on the skeleton by FM and by the effect of different hormones. The aim of the present study was to determine whether there is a relationship between ghrelin, adiponectin, and leptin with BMC and BMD in healthy postmenopausal women (n = 88; age, 68.9 +/- 6.8 years; body mass index, 27.4 +/- 3.6 kg/m(2)). Body composition, BMC, and BMD were derived by dual-energy X-ray absorptiometry. Waist-to-hip (WHR) and waist-to-thigh (WTR) ratios were also obtained. Ghrelin was associated with total BMC (beta = -0.945; P = 0.0001), total BMD (beta = -0.959; P = 0.0001), lumbar spine BMD (beta = -0.945; P = 0.0001), and femoral neck BMD (beta = -0.957; P = 0.0001), and remained associated (P 0.041) in different analyses that controlled for measured body composition and hormonal and insulin resistance values. However, the associations between ghrelin and measured bone mineral values were no longer significant (P 0.149) when adjusted for body fat distribution values (WHR, WTR). Adiponectin was significantly related to total BMC (beta = -0.931; P = 0.0001), total BMD (beta = -0.940; P = 0.0001), lumbar spine BMD (beta = -0.937; P = 0.0001), and femoral neck BMD (beta = -0.940; P = 0.0001) values, and these relationships remained significant (P 0.019) after adjusting for measured body fat, hormonal, and insulin resistance values but not when adjusted for fat-free mass (FFM; P 0.106). In addition, significant associations of leptin with total BMC (beta = 0.912; P = 0.0001), total BMD (beta = 0.907; P = 0.0001), lumbar spine BMD (beta = 0.899; P = 0.0001), and femoral neck BMD (beta = 0.906; P = 0.0001) were found. These associations remained significant (P 0.010) in different analyses that controlled for hormonal and insulin resistance values, but the associations between leptin and bone mineral values were no longer significant (P 0.145) when adjusted for specific body composition values (WHR, WTR, FM, and FFM). In conclusion, it appears that the influence of plasma ghrelin, adiponectin, and leptin levels on BMC and BMD values is mediated or confounded by the specific body composition parameters in healthy postmenopausal women.
    Tipo de documento:
    Referencia
    Referencia del producto:
    HADP-61HK
    Nombre del producto:
    Human Adiponectin RIA
  • The circadian clock modulates enamel development. 22653892

    Fully mature enamel is about 98% mineral by weight. While mineral crystals appear very early during its formative phase, the newly secreted enamel is a soft gel-like matrix containing several enamel matrix proteins of which the most abundant is amelogenin (Amelx). Histological analysis of mineralized dental enamel reveals markings called cross-striations associated with daily increments of enamel formation, as evidenced by injections of labeling dyes at known time intervals. The daily incremental growth of enamel has led to the hypothesis that the circadian clock might be involved in the regulation of enamel development. To identify daily rhythms of clock genes and Amelx, we subjected murine ameloblast cells to serum synchronization to analyze the expression of the circadian transcription factors Per2 and Bmal1 by real-time PCR. Results indicate that these key genetic regulators of the circadian clock are expressed in synchronized murine ameloblast cell cultures and that their expression profile follows a circadian pattern with acrophase and bathyphase for both gene transcripts in antiphase. Immunohistological analysis confirms the protein expression of Bmal and Cry in enamel cells. Amelx expression in 2-day postnatal mouse molars dissected every 4 hours for a duration of 48 hours oscillated with an approximately 24-hour period, with a significant approximately 2-fold decrease in expression during the dark period compared to the light period. The expression of genes involved in bicarbonate production (Car2) and transport (Slc4a4), as well as in enamel matrix endocytosis (Lamp1), was greater during the dark period, indicating that ameloblasts express these proteins when Amelx expression is at the nadir. The human and mouse Amelx genes each contain a single nonconserved E-box element within 10 kb upstream of their respective transcription start sites. We also found that within 2 kb of the transcription start site of the human NFYA gene, which encodes a positive regulator of amelogenin, there is an E-box element that is conserved in rodents and other mammals. Moreover, we found that Nfya expression in serum-synchronized murine ameloblasts oscillated with a strong 24-hour rhythm. Taken together, our data support the hypothesis that the circadian clock temporally regulates enamel development.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB4140
    Nombre del producto:
    Anti-MOP3 Antibody
  • Novel mineral contrast agent for magnetic resonance studies of bone implants grown on a chick chorioallantoic membrane. 21920685

    Magnetic resonance imaging (MRI) studies of tissue engineered constructs prior to implantation clearly demonstrate the utility of the MRI technique for studying the bone formation process. To test the utility of our MRI protocols for explant studies, we present a novel test platform in which osteoblast-seeded scaffolds were implanted on the chorioallantoic membrane of a chick embryo. Scaffolds from the following experimental groups were examined by high-resolution MRI: (a) cell-seeded implanted scaffolds (CIM), (b) unseeded implanted scaffolds (UCIM), (c) cell-seeded scaffolds in static culture (CIV) and (d) unseeded scaffolds in static culture (UCIV). The reduction in water proton transverse relaxation times and the concomitant increase in water proton magnetization transfer ratios for CIM and CIV scaffolds, compared to UCIV scaffolds, were consistent with the formation of a bone-like tissue within the polymer scaffold, which was confirmed by immunohistochemistry and fluorescence microscopy. However, the presence of angiogenic vessels and fibrotic adhesions around UCIM scaffolds can confound MRI findings of bone deposition. Consequently, to improve the specificity of the MRI technique for detecting mineralized deposits within explanted tissue engineered bone constructs, we introduce a novel contrast agent that uses alendronate to target a Food and Drug Administration-approved MRI contrast agent (Gd-DOTA) to bone mineral. Our contrast agent termed GdALN was used to uniquely identify mineralized deposits in representative samples from our four experimental groups. After GdALN treatment, both CIM and CIV scaffolds, containing mineralized deposits, showed marked signal enhancement on longitudinal relaxation time-weighted (T1W) images compared to UCIV scaffolds. Relative to UCIV scaffolds, some enhancement was observed in T1W images of GdALN-treated UCIM scaffolds, subjacent to the dark adhesions at the scaffold surface, possibly from dystrophic mineral formed in the fibrotic adhesions. Notably, residual dark areas on T1W images of CIM and UCIM scaffolds were attributable to blood inside infiltrating vessels. In summary, we present the efficacy of GdALN for sensitizing the MRI technique to the deposition of mineralized deposits in explanted polymeric scaffolds.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB752P
    Nombre del producto:
    Anti-Collagen Type I Antibody
  • Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells. 22260151

    Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear.As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells treated with low doses of ZOL (10 μM). Microarrays analysis was used to identify, describe and summarize evidence regarding the molecular basis of actions of ZOL and of their possible direct anti-tumour effects. We validated gene expression results of specific transcripts involved in major cellular process by Real Time and Western Blot analysis and we observed inhibition of proliferation and migration through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Matrigel assay. We then focused on changes in the cytoskeletal components as fibronectin 1 (FN1), actin, and anti angiogenic compounds as transforming growth factor-β1 (TGF-β1) and thrombospondin 1 (THBS1). The up-regulation of these products may have an important role in inhibiting proliferation, invasion and angiogenesis mediated by ZOL.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB1132
  • Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density. 18924182

    Osteoporosis (OP) is a major public health problem, mainly characterized by low bone mineral density (BMD). Circulating monocytes (CMCs) may serve as progenitors of osteoclasts and produce a wide variety of factors important to bone metabolism. However, the specific action mechanism of CMCs in the pathogenesis of OP is far from clear. We performed a comparative protein expression profiling study of CMCs in Chinese premenopausal females with extremely discordant BMD, identified a total of 38 differentially expressed proteins, and confirmed with Western blotting five proteins: ras suppressor protein1 (RSU1), gelsolin (GSN), manganese-containing superoxide dismutase (SOD2), glutathione peroxidase 1(GPX1), and prolyl 4-hydroxylase beta subunit (P4HB). These proteins might affect CMCs' trans-endothelium, differentiation, and/or downstream osteoclast functions, thus contribute to differential osteoclastogenesis and finally lead to BMD variation. The findings promote our understanding of the role of CMCs in BMD determination, and provide an insight into the pathogenesis of human OP.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB2073
  • Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables. 17341545

    The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but 7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) 30 kg/m(2). Adiponectin values were higher (P 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.
    Tipo de documento:
    Referencia
    Referencia del producto:
    HADP-61HK
    Nombre del producto:
    Human Adiponectin RIA