353 research outputs found
The Orphan Nuclear Estrogen Receptor–Related Receptor α (Errα) Is Expressed Throughout Osteoblast Differentiation and Regulates Bone Formation in Vitro
The orphan nuclear estrogen receptor–related receptor α (ERRα), is expressed by many cell types, but is very highly expressed by osteoblastic cells in which it transactivates at least one osteoblast-associated gene, osteopontin. To study the putative involvement of ERRα in bone, we first assessed its expression in rat calvaria (RC) in vivo and in RC cells in vitro. ERRα mRNA and protein were expressed at all developmental stages from early osteoprogenitors to bone-forming osteoblasts, but protein was most abundant in mature cuboidal osteoblasts. To assess a functional role for ERRα in osteoblast differentiation and bone formation, we blocked its expression by antisense oligonucleotides in either proliferating or differentiating RC cell cultures and found inhibition of cell growth and a proliferation-independent inhibition of differentiation. On the other hand, ERRα overexpression in RC cells increased differentiation and maturation of progenitors to mature bone-forming cells. Our findings show that ERRα is highly expressed throughout the osteoblast developmental sequence and plays a physiological role in differentiation and bone formation at both proliferation and differentiation stages. In addition, we found that manipulation of receptor levels in the absence of known ligand is a fruitful approach for functional analysis of this orphan receptor and identification of potential target genes
Leptonic decay constants f_Ds and f_D in three flavor lattice QCD
We determine the leptonic decay constants in three flavor unquenched lattice
QCD. We use O(a^2)-improved staggered light quarks and O(a)-improved charm
quarks in the Fermilab heavy quark formalism. Our preliminary results, based
upon an analysis at a single lattice spacing, are f_Ds = 263(+5-9)(+/-24) MeV
and f_D = 225(+11-13)(+/-21) MeV. In each case, the first reported error is
statistical while the is the combined systematic uncertainty.Comment: Talk presented at Lattice2004(heavy), Fermilab, June 21-26, 2004. 3
pages, 2 figure
Pion and kaon physics with improved staggered quarks
We compute pseudoscalar meson masses and decay constants using staggered
quarks on lattices with three flavors of sea quarks and lattice spacings
fm and fm. We fit partially quenched results to
``staggered chiral perturbation theory'' formulae, thereby taking into account
the effects of taste-symmetry violations. Chiral logarithms are observed. From
the fits we calculate and , extract Gasser-Leutwyler parameters of
the chiral Lagrangian, and (modulo rather large perturbative errors) find the
light and strange quark masses.Comment: Lattice2003(spectrum); 3 pages, 1 eps figur
Charmed meson decay constants in three-flavor lattice QCD
We present the first lattice QCD calculation with realistic sea quark content
of the D^+ meson decay constant f_{D^+}. We use the MILC Collaboration's
publicly available ensembles of lattice gauge fields, which have a quark sea
with two flavors (up and down) much lighter than a third (strange). We obtain
f_{D^+} = 201 +/- 3 +/- 17 MeV, where the errors are statistical and a
combination of systematic errors. We also obtain f_{D_s} = 249 +/- 3 +/- 16 MeV
for the D_s meson.Comment: note added on recent CLEO measurement; PRL versio
Measurement of the branching ratio of the decay D^0 -> \pi^-\mu^+\nu relative to D^0 -> K^-\mu^+\nu
We present a new measurement of the branching ratio of the Cabibbo suppressed
decay D^0\to \pi^-\mu^+\nu relative to the Cabibbo favored decay D^0\to
K^-\mu^+\nu and an improved measurement of the ratio
|\frac{f_+^{\pi}(0)}{f_+^{K}(0)}|. Our results are 0.074 \pm 0.008 \pm 0.007
for the branching ratio and 0.85 \pm 0.04 \pm 0.04 \pm 0.01 for the form factor
ratio, respectively.Comment: 13pages, 3 figure
Biological response to pre-mineralized starch based scaffolds for bone tissue engineering
It is known that calcium-phosphate (Ca-P) coatings are able not only to improve the bone
bonding behaviour of polymeric materials, but at the same time play a positive role on
enhancing cell adhesion and inducing the differentiation of osteoprogenitor cells. Recently
an innovative biomimetic methodology, in which a sodium silicate gel was used as a
nucleative agent, was proposed as an alternative to the currently available biomimetic
coating methodologies. This methodology is especially adequate for coating biodegradable
porous scaffolds. In the present work we evaluated the influence of the referred to
treatment on the mechanical properties of 50/50 (wt%) blend of corn starch/ethylene-vinyl
alcohol (SEVA-C) based scaffolds. These Ca-P coated scaffolds presented a compressive
modulus of 224.6 ± 20.6 and a compressive strength of 24.2 ± 2.20. Cytotoxicity evaluation
was performed according ISO/EN 10993 part 5 guidelines and showed that the biomimetic
treatment did not have any deleterious effect on L929 cells and did not inhibit cell growth.
Direct contact assays were done by using a cell line of human osteoblast like cells (SaOS-2).
3 × 105 cells were seeded per scaffold and allowed to grow for two weeks at 37 ◦C in a
humidified atmosphere containing 5% CO2. Total protein quantification and scanning
electron microscopy (SEM) observation showed that cells were able to grow in the
pre-mineralized scaffolds. Furthermore cell viability assays (MTS test) also show that cells
remain viable after two weeks in culture. Finally, protein expression studies showed that
after two weeks osteopontin and collagen type I were being expressed by SaOS-2 cells
seeded on the pre-mineralized scaffolds. Moreover, alkaline phosphatase (ALP) activity was
higher in the supernatants collected from the pre-mineralized samples, when compared to
the control samples (non Ca-P coated). This may indicate that a faster mineralization of the
ECM produced on the pre-mineralized samples was occurring. Consequently, biomimetic
pre-mineralization of starch based scaffolds can be a useful route for applying these
materials on bone tissue engineering
Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone
Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro. Increased levels of ERRα in tumor cells led to rapid tumor progression, with both bone destruction and formation, and direct impacts on osteoclasts and osteoblasts. VEGF-A, WNT5A and TGFβ1 were upregulated by ERRα in tumor cells and all of these factors also significantly and positively correlated with ERRα expression in CRPC patient specimens. Finally, high levels of ERRα in tumor cells stimulated the pro-metastatic factor periostin expression in the stroma, suggesting that ERRα regulates the tumor stromal cell microenvironment to enhance tumor progression. Taken together, our data demonstrate that ERRα is a regulator of CRPC cell progression in bone. Therefore, inhibiting ERRα may constitute a new therapeutic strategy for prostate cancer skeletal-related events
Measurements of the qsq dependence of the D0 to K mu nu and D0 to pi mu nu form factors
Using a large sample of D0 to K mu nu and pi mu nu decays collected by the
FOCUS photoproduction experiment at Fermilab, we present new measurements of
the q^2 dependence for the f+(q^2) form factor. These measured f+(q^2) form
factors are fit to common parameterizations such as the pole dominance form and
compared to recent unquenched Lattice QCD calculations. We find m_pole =
1.93+-0.05+-0.03 GeV/c^2 for D0 to K mu nu and m_pole = 1.91+0.30-0.15+-0.07
GeV/c^2 for D0 to pi mu nu and f-^{K}(0)/f+^{K}(0) = -1.7+1.5-1.4+-0.3.Comment: 14 pages, 6 figure
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