1,721,014 research outputs found
Global Transcriptome Analysis in Mouse Osteoblasts Identifies a Mechanosensing Osteoblast Gene Signature
No full textGlobal Transcriptome Analysis in Mouse Calvarial Osteoblasts Highlights Sets of Genes Regulated by Modeled Microgravity and Identifies A "Mechanoresponsive Osteoblast Gene Signature"
No full textMechanical unloading is known to be detrimental for the skeleton, but the underlying molecular mechanisms are not fully elucidated. We performed global transcriptome analysis of mouse calvarial osteoblasts grown for 5 days at unit gravity (1g) or under modeled microgravity (0.008g) in the NASA-developed rotating wall vessel (RWV) bioreactor. Elaboration of gene profiling data evidenced that, among the >20,000 gene probes evaluated, 45 genes were significantly up-regulated (cut-off >2) and 88 were down-regulated (cut-off <0.5) in modeled microgravity versus 1g. This set of regulated genes includes genes involved in osteoblast differentiation, function, and osteoblast-osteoclast cross-talk, as well as new genes not previously correlated with bone metabolism. Microarray data were validated for subsets of genes by real-time RT-PCR, Western blot, or functional analysis. The significantly modulated genes were then clustered using the GOTM (Gene Ontology Tree Machine) software. This analysis evidenced up-regulation of genes involved in the induction of apoptosis, in response to stress and in the activity of selected growth factors. Other molecular functions, such as extracellular matrix structural constituent, glycosaminoglycan/heparin-binding activity, and other growth factor activity, were instead down-regulated. We finally matched our transcriptome results with other public global gene profiles obtained in loading and unloading conditions, identifying 10 shared regulated genes which could represent an "osteoblast mechanoresponsive gene signature." J. Cell. Biochem. 107:240-252, 2009. (C) 2009 Wiley-Liss, Inc
Role of RAMP2 and BSP2 in the c-Src-regulated osteomimicry of breast cancer bone metastasis
No full textthe effect of microgravity on osteoblast metabolism
No full textSeveral reports have shown the deleterious effects of weightlessness on astronauts. Among
the pathological conditions recorded, those involving the skeleton are dramatic,
characterised by a decrease of bone mass and by bone demineralization, eventually leading
to osteoporosis. This is consistent with the notion that mechanical loading is critical for the
maintenance of a correct bone mass, since it has an anabolic effect by activating bone
formation and inhibiting bone resorption. Space flight experiments, as well as ground-based
studies performed using different models of simulated microgravity, demonstrated that
bone loss could, at least in part, be due to a decrease in bone formation by osteoblasts, the
cells of the bone tissue devoted to build the bone matrix. Interestingly, it seems that
osteoblasts themselves are directly sensitive to the reduced gravity force, which in turn acts
by impairing their differentiation and function, as demonstrated by a decrease of the
expression of the osteoblast master gene runx2 and of the specific osteoblast marker ALP,
along with a decrease of the production of the bone matrix proteins osteocalcin, collagen 1
alpha 1 and osteopontin. Consistently, weightlessness also induced a reduction of osteoblast
life-span and an increase of apoptosis. Based on this evidence, there is the need to more
deeply investigate the molecular mechanisms underlying weightlessness-induced bone loss,
in order to identify new molecular targets for alternative therapies, useful to counteract the
deleterious effects of weightlessness in astronauts as well as to cure pathological conditions
of reduced bone mass on earth
Gene microarray analysis in mouse osteoblasts reveals sets of relevant mrnas regulated under modeled microgravity
No full textSMALL INTERFERING RNA (siRNA) FOR THE THERAPY OF TYPE 2 (ADO2) AUTOSOMAL DOMINANT OSTEOPETROSIS CAUSED BY CLCN7 (ADO2 CLCN7-DEPENDENT) GENE MUTATION
No full textMultidisciplinary investigation of an ancient renal stone in a mummy from Popoli, central Italy
Full text linkThe renal stone found in the natural mummy of an anonymous nobleman dating to 19(th) century was investigated using advanced imaging modalities and analytic investigations. By this multidisciplinary approach we were able to identify the chemical components and their distribution throughout the sample. These results allowed to understand the lifestyle habits of the subject, as well as the exact pathogenesis of his disease
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