1,721,026 research outputs found
The extracellular matrix (ECM) component prelp(proline/arginine-rich end leucine-rlch repeat protein inhibits osteoclastogenesis
No full textModeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio
No full textMechanical unloading causes detrimental effects on the skeleton, but the underlying mechanisms are still unclear. We investigated the effect of microgravity on osteolblast ability to regulate osteoclastogenesis. Mouse osteoblast primary cultures were grown for 24 h at unit gravity or under simulated microgravity, using the NASA-developed Rotating Wall Vessel bioreactor. Conditioned media (CM) from osteoblasts subjected to microgravity increased osteoclastogenesis and bone resorption in mouse bone marrow cultures. In these osteoblasts, the RANKL/OPG ratio was higher relative to 1g. Consistently, treatment with high concentrations of OPG-inhibited osteoclastogenesis and bone resorption in the presence of CM arising from osteoblasts Cultured Linder microgravity. Microgravity failed to affect osteoblast differentiation and function in the time frame of the experiment, as we found no effect on alkaline phosphatase mRNA and activity, nor on Runx2, osteocalcin, osteopontin, and collagen1A2 mRNA expression. In contrast, microgravity induced a time dependent increase of ERK-1/2 phosphorylation, while phospho-p38 and phospho-JNK remained unchanged. Apoptosis, revealed by bis-benzimide staining, was similar among the various gravity conditions, while it was increased under microgravity after treatment with the MEK-1/2 inhibitor, PD98059, suggesting a protection role by ERK-1/ 2 against cell death. In conclusion, microgravity is capable to indirectly Stimulate osteoclast formation and activity by regulating osteoblast secretion of crucial regulatory factors such as RANKL and OPG. We hypothesize that this mechanism could contribute to bone loss in individuals subjected to weightlessness and other unloading conditions
the 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
The matrix PRoline/arginine-rich end leucine-rich repeat protein (PRELP) inhibits osteoclastogenesis inactivating the NF-kappaB signal
No full textMolecular mechanisms enhancing osteoclastogenesis and bone resorption under modeled microgravity.
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Global 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
Global Transcriptome Analysis in Mouse Osteoblasts Identifies a Mechanosensing Osteoblast Gene Signature
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