1%), followed by urge incontinence, which was seen in 29 (80 5%)

1%), followed by urge incontinence, which was seen in 29 (80.5%). Compared to baseline, urinary symptoms were substantially improved. The negative impact of storage symptoms on quality

of life was significantly decreased from a mean +/- SD of 3.3 +/- 1.7 to 0.5 +/- 0.9 (p <0.001). Mean +/- SD maximum urinary flow improved from 14.2 +/- 15.0 to 20.5 +/- 6.4 ml per second (p <0.001).

Conclusions: A total of 12 weeks of therapy with selleck kinase inhibitor 0.6 mg/kg oxybutynin daily resulted in improvement of lower urinary tract symptoms, quality of life and maximum flow rate in most patients with Williams-Beuren syndrome.”
“Soybean calmodulin isoform 4 (sCaM4) is a plant calcium-binding protein, regulating cellular responses to the second messenger Ca2+. We have found that the metal ion free (apo-) form of sCaM4 possesses a half unfolded structure, with the N-terminal domain unfolded and the C-terminal domain folded. This result was unexpected as the apo-forms of both soybean calmodulin isoform 1 (sCaM1) and mammalian CaM (mCaM) are fully folded. Because of the fact

that free QNZ cell line Mg2+ ions are always present at high concentrations in cells (0.5-2 mM), we suggest that Mg2+ should be bound to sCaM4 in nonactivated cells. CD studies revealed that in the presence of Mg2+ the initially unfolded N-terminal domain of sCaM4 folds into an alpha-helix-rich structure, similar to the Ca2+ form. We have used the NMR backbone residual dipolar coupling restraints D-1(NH), D-1(C alpha H alpha), and D-1(c’c alpha) to determine the solution structure of the N-terminal domain of Mg2+ -sCaM4 (Mg2+-sCaM4-NT). Compared with the known structure of Ca2+ -sCaM4, the structure of the Mg2+- sCaM4-NT does not fully open the hydrophobic pocket, which was further confirmed by the use of the fluorescent probe ANS. Tryptophan fluorescence experiments were used to study the interactions between Mg(2+)sCaM4 and CaM-binding peptides derived from smooth muscle myosin light chain kinase and plant glutamate decarboxylase. These results suggest that Mg2+-sCaM4 does not bind to Ca2+-CaM target peptides almost and therefore is functionally similar to apo-mCaM. The

Mg2+- and apo-structures of the sCaM4-NT provide unique insights into the structure and function of some plant calmodulins in resting cells.”
“Nonsuicidal self-injury (NSSI), or the purposeful destruction of body tissue occurring without suicidal intent, is a perplexing behavior as it goes against the natural instinct to maximize pleasure and minimize pain. One possible reason that people engage in NSSI is to regulate affect. However, the exact mechanisms that cause NSSI to lead to reduced feelings of negative affect remain unclear. Due to its involvement in the regulation of pain and emotion, the endogenous opioid system has been proposed to mediate the affect regulation effects of NSSI. The authors review evidence from multiple literatures to support this claim.

(c) 2009 Elsevier Ltd All rights reserved “
“Accumulating e

(c) 2009 Elsevier Ltd. All rights reserved.”
“Accumulating evidence suggests that urokinase plasminogen activator (uPA) is involved in vascular remodeling and lumen stenosis after angioplasty and stenting. We have shown previously that increased uPA expression greatly promotes neointima formation

and inward arterial remodeling after balloon injury. To evaluate the role of inflammation in early mechanisms responsible for inward arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we characterized changes in the expression profiles of 8,799 genes in injured rat carotid arteries 1 and 4 days after recombinant https://www.selleckchem.com/products/jsh-23.html uPA treatment compared to vehicle. We used a standard model of the balloon catheter injury of the rat carotid followed by periadventitial application to the injured vessel of either uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed by immunohistochemistry, morphometry, microarray gene expression profiling and quantitative RT-PCR. Periadventitial

application of uPA significantly reduced lumen size and vessel area encompassed by the external elastic ARS-1620 lamina at both 1 and 4 days after treatment. Inflammatory cells accumulated in the arterial adventitia at both 1 and 4 days after uPA treatment. On the 4th day, increases in the areas and arterial cell numbers of all arterial layers were found. Among 79 differentially expressed known genes 1 day after uPA application, 12 proinflammatory genes, including TNF-alpha and TACE, and 15 genes related to mitochondrial metabolism and oxidative stress regulation were identified. Four days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation-related genes were

differentially expressed. We conclude that uPA likely promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury. Copyright (c) 2008 S. Karger AG, Basel”
“Selective sparing of abstract relative to concrete words has been documented only exceptionally in aphasia, Etofibrate following bilateral temporal damage. In this paper we present a new case with sparing of abstract word processing and impairment of concrete words due to selective atrophy of the left anterior temporal regions.

In our subject, the reversal of the concreteness effect was restricted to nouns. Performance on nouns was not homogeneous. Proper names (people and landmarks) were very severely damaged. Among common names, living entities were selectively impaired in comparison to non-living entities. Category-specific damage for living beings resulted from widespread loss of conceptual information, and perceptual information was less impaired than associative knowledge. This observation challenges theories explaining the reversal of concreteness effect with a selective loss of perceptual information.

Thus, these two responses to different forms of LPS exposure are

Thus, these two responses to different forms of LPS exposure are significantly correlated, and more responsive monocytes in vitro indicate a forthcoming relative monocytosis, post barn exposure, which may initiate a cascade of chronic inflammation.”
“The relative activity factor (RAF) was used to predict the contribution of different cytochrome P-450 (CYP) 3A isoforms (3A1 and 3A2 in rat liver microsomes and 3A4 and 3A5 in human liver microsomes) to 4beta-C hydroxylation of territrem A (TRA). Seven recombinant rat and eight recombinant human CYP450 isoforms, five rat liver microsomes, and seven human liver microsomes were assessed. this website In liver microsomes from five male Wistar rats, TRA 4beta-C

hydroxylation activity significantly correlated with CYP3A1/2 activity, while, in liver microsomes from seven humans, there was marked correlation with CYP3A4 activity. Immunoinhibition confirmed that CYP3A2 and CYP3A4 were responsible for the hepatic metabolism of TRA 4beta-C hydroxylation. Using RAF, the percent contributions of CYP3A1 and

Vistusertib in vivo CYP3A2 to 4beta-C hydroxylation of TRA in rat liver microsomes were estimated as 5 to 6 and 94 to 96, respectively, and those of CYP3A4 and CYP3A5 in human liver microsomes as 70 to 72 and 28 to 30%, respectively. These results suggest that CYP3A2 and CYP3A4 are the main form involved in the 4beta-C hydroxylation of TRA in rat and human liver microsomes.”
“Splenda is comprised of the high-potency

Sclareol artificial sweetener sucralose (1.1%) and the fillers maltodextrin and glucose. Splenda was administered by oral gavage at 100, 300, 500, or 1000 mg/kg to male Sprague-Dawley rats for 12-wk, during which fecal samples were collected weekly for bacterial analysis and measurement of fecal pH. After 12-wk, half of the animals from each treatment group were sacrificed to determine the intestinal expression of the membrane efflux transporter P-glycoprotein (P-gp) and the cytochrome P-450 (CYP) metabolism system by Western blot. The remaining animals were allowed to recover for an additional 12-wk, and further assessments of fecal microflora, fecal pH, and expression of P-gp and CYP were determined. At the end of the 12-wk treatment period, the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria were significantly decreased; however, there was no significant treatment effect on enterobacteria. Splenda also increased fecal pH and enhanced the expression of P-gp by 2.43-fold, CYP3A4 by 2.51-fold, and CYP2D1 by 3.49-fold. Following the 12-wk recovery period, only the total anaerobes and bifidobacteria remained significantly depressed, whereas pH values, P-gp, and CYP3A4 and CYP2D1 remained elevated. These changes occurred at Splenda dosages that contained sucralose at 1.1-11 mg/kg (the US FDA Acceptable Daily Intake for sucralose is 5 mg/kg).

Furthermore, intra-dPAG MK-212

(63 6 nmol) showed an anxi

Furthermore, intra-dPAG MK-212

(63.6 nmol) showed an anxiolytic-like effect on both Trial I and Trial 2. Importantly, these effects were observed in the absence of any significant change in closed arm entries, the parameter considered to be a valid index of locomotor activity in the plus-maze. These results support the dPAG as a crucial structure involved in the neurobiology of the OTT phenomenon as well as accounting the role of the 5-HT(2A) and 5-HT(2C) receptors located within this midbrain structure on the emotional state induced by EPM test and retest paradigm mice. (C) 2009 Elsevier Inc. All rights reserved.”
“BACKGROUND

Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; https://www.selleckchem.com/products/azd6738.html treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA.

METHODS

We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration

of >= 6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was >= 30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo Cytoskeletal Signaling inhibitor given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension.

RESULTS

At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab http://www.selleck.co.jp/products/Decitabine.html had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with

active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range.

CONCLUSIONS

Tocilizumab was efficacious in severe, persistent systemic JIA.

In SM1, finger movements

In SM1, finger movements Peptide 17 order (10,809) induced more activation than toe movements (5349). On the other hand, in the PMA and PFC, toe movements (PMA: 4201, PFC: 921) induced more activation than finger movements (PMA: 2887, PFC: 912) respectively. In the analysis of relative voxel counts in the PMA and PFC versus the SM1, toe movements generated more activation in the PMA and PFC than finger movements. The PMA and PFC were more activated by toe than finger movements, although the SM1 was more activated by finger movements. (c) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Poxvirus acquires its primary envelope through a process that is distinct from those of other enveloped viruses. The

molecular mechanism of this process is poorly understood, but several poxvirus proteins essential for the process have been identified in studies of vaccinia virus (VACV), the prototypical poxvirus. Previously, we identified VACV A6 as an essential factor for virion morphogenesis

by studying a temperature-sensitive mutant with a lesion in A6. Here, we further studied A6 by constructing and characterizing an inducible virus (iA6) that could more stringently repress A6 expression. When A6 expression was induced by the inducer isopropyl-beta-D-thiogalactoside (IPTG), iA6 replicated normally, and membrane proteins of mature virions (MVs) predominantly localized in viral factories where virions were assembled. However, when Selleckchem AZD6244 A6 expression was repressed, electron microscopy of infected cells showed the accumulation of large viroplasm inclusions containing virion core proteins but no viral membranes. Immunofluorescence and cell fractionation studies showed that the major MV membrane proteins A13, A14,

D8, and H3 did not localize to viral factories but instead accumulated in the secretory compartments, including the endoplasmic reticulum. Overall, our results show that A6 is an additional VACV protein that participates in an early step of virion membrane biogenesis. Furthermore, A6 is required for MV membrane protein localization to sites of virion assembly, suggesting that MV membrane proteins or precursors of MV membranes are trafficked to sites of virion assembly through an active, virus-mediated process that requires A6.”
“The concept of ‘cognitive ID-8 reserve’, and a broader theory of ‘brain reserve’, were originally proposed to help explain epidemiological data indicating that individuals who engaged in higher levels of mental and physical activity via education, occupation and recreation, were at lower risk of developing Alzheimer’s disease and other forms of dementia. Subsequently, behavioral, cellular and molecular studies in animals (predominantly mice and rats) have revealed dramatic effects of environmental enrichment, which involves enhanced levels of sensory, cognitive and motor stimulation via housing in novel, complex environments.

Only a few nonenveloped nucleocapsids were found in the axon The

Only a few nonenveloped nucleocapsids were found in the axon. The same picture was observed after infection by phenotypically complemented gB-deficient PrV, which is able to complete only a single round of replication. Our data thus support intraaxonal anterograde transport of enveloped PrV virions Eltanexor within vesicles following the “”married model.”"”
“Effective HIV-specific T-cell immunity requires the ability to inhibit virus replication in the infected host, but the functional characteristics of cells able to mediate

this effect are not well defined. Since Gag-specific CD8 T cells have repeatedly been associated with lower viremia, we examined the influence of Gag specificity on the ability of unstimulated CD8 T cells from chronically infected Fedratinib chemical structure persons to inhibit virus replication in autologous CD4 T cells. Persons with broad (>= 6; n = 13) or narrow (<= 1; n = 13) Gag-specific responses, as assessed by gamma interferon enzyme-linked immunospot assay, were selected from 288 highly active antiretroviral therapy (HAART)-naive HIV-1 clade C-infected South Africans, matching groups for total magnitude of HIV-specific CD8 T-cell responses and CD4 T-cell counts. CD8 T cells from high Gag responders

suppressed in vitro replication of a heterologous HIV strain in autologous CD4 cells more potently than did those from low Gag responders (P < 0.003) and were associated with lower viral loads in vivo (P < 0.002). As previously shown Astemizole in subjects with low viremia, CD8 T cells from high Gag responders exhibited a more polyfunctional cytokine profile

and a stronger ability to proliferate in response to HIV stimulation than did low Gag responders, which mainly exhibited monofunctional CD8 T-cell responses. Furthermore, increased polyfunctionality was significantly correlated with greater inhibition of viral replication in vitro. These data indicate that enhanced suppression of HIV replication is associated with broader targeting of Gag. We conclude that it is not the overall magnitude but rather the breadth, magnitude, and functional capacity of CD8 T-cell responses to certain conserved proteins, like Gag, which predict effective antiviral HIV-specific CD8 T-cell function.”
“Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible for inducing these changes is known. Feline junctional adhesion molecule A (fJAM-A) mediates the attachment and infectious viral entry of feline calicivirus (FCV). Here, we show that the infectivity of some FCV isolates is neutralized following incubation with the soluble receptor at 37 degrees C.

0% for remote control areas (P<0 001) Based on triphenyltetra

0% for remote control areas (P<0.001). Based on triphenyltetrazolium chloride staining and autoradiograph image data, the hotspot uptake may be associated primarily with the ischemic penumbra, in which high apoptotic activity was observed by cleaved caspase-3 immunocytochemical staining.

Conclusions: Tc-99m-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury. (C) 2013 Elsevier Inc. All rights reserved.”
“The double-hit hypothesis posits that an early

life genetic or environmental insult sets up a neural predisposition Linsitinib to psychopathology, which may emerge in the presence of a subsequent insult, or ‘second hit’ in later life. The current study assessed the effect of neonatal lipopolysaccharide (LPS) exposure on anxiety-like behaviours in the adult Wistar rat. Rats were administered either LPS (Salmonella enterica, serotype enteritidis, 0.05 mg/kg, ip) or saline (equivolume) on days 3 and 5 of life (birth = day 1). In adulthood (85 days), subjects were allocated to either “”stress”" or “”no stress”" treatment groups. For the “”stress”" group, subjects were exposed to a three-day stress protocol consisting of a 30 min period of restraint and isolation. The “”no stress”" group was left unperturbed but were handled during this period to control for handling effects between adult “”stress”" and “”no stress”"

conditions. All animals then underwent behavioural testing using standardised tests of selleck inhibitor anxiety-like behaviour, including either the Hide Box/Open Field, Elevated Plus Maze (EPM) or Acoustic Startle Response (ASR). Time and event measures for restraint and isolation, the Hide Box/Open Field and EPM were recorded using automated tracking software. Startle amplitude and habituation across time was measured in the ASR test. Prior to and following behavioural test sessions, peripheral blood was

collected to assess serum corticosterone and ACTH levels. Data analysis indicated that LPS-treated animals exposed to stress in adulthood exhibited increased from anxiety-like behaviour across all behavioural tests compared to controls. Sexually dimorphic effects were observed with mates exhibiting increased anxiety-related behaviours compared to females (p<.05). Neonatal LPS exposure induced a significant increase in corticosterone compared to controls (p<.05), whereas corticosterone responses to stress in adulthood were associated with a significantly blunted HPA axis response (p<.05). No differences in ACTH were observed. These results tend support to the double-hit hypothesis of anxiety-related behaviour, demonstrating that neonatal immune activation produces an enhanced propensity toward anxiety-related behaviour following stress in adulthood, and that this susceptibility is associated with alterations to HPA axis ontogeny. (C) 2009 Elsevier Ltd. All rights reserved.”
“The projected effects of the new biology on future medicine are described.

The HE possesses receptor binding and receptor destroying enzyme

The HE possesses receptor binding and receptor destroying enzyme (RDE) activity and is probably involved in the infection process.

The recombinant HE protein (recHE 4) was expressed in insect cells (Sf9) using the baculovirus expression vector system. Both the transmembrane region and the cytoplasmic tail were deleted, and a C-terminal

His(6)-tag was attached to facilitate identification and purification of the recHE 4 protein. As determined by Western analysis this website the recHE 4 was secreted at 20 degrees C and not at 28 degrees C. By testing three HE constructs differing in their promoter and secretion signal sequences it was clear that the HE’s own secretion signal sequence is more important than the promoter with respect to the amount of secreted recHE selleck products 4 obtained under the conditions used. A one-step purification by nickel-affinity chromatography resulted in a highly purified recHE 4, identified

by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. Also, the recHE 4 is glycosylated and contains disulfide bridges within the molecule. Functional studies including the verification of the receptor destroying enzyme (RDE) activity as well as the binding to Atlantic salmon erythrocytes (hemagglutination) indicate that the recHE 4 has similar functions as its native counterpart.

In conclusion, insect cells secrete a functional form of the ISAV 4 HE. This is suitable for further analyses on its function and immunogenicity. (c) 2008 Elsevier Inc. All rights reserved.”
“The mammalian brain commonly uses structural proximity to reflect proximity in stimulus and perceptual space. Objects or object features that are near each other in GPX6 physical structure or perception are also near each other in the brain. This generates sensory maps. The topography of olfactory connectivity implies a rudimentary map in the olfactory

epithelium, a more intricate map in the olfactory bulb, but no ordered topography is evident in piriform cortex. Currently, we are largely unable to link the ordered topography in epithelium and bulb to meaningful olfactory axes within a strong predictive framework. We argue that the path to uncovering such a predictive framework depends on systematically characterizing olfactory perception, and we describe initial efforts in this direction.”
“Curiosity is a cornerstone of cognition that has the potential to lead to innovations and increase the behavioral repertoire of individuals. A defining characteristic of curiosity is inquisitiveness directed toward novel objects. Species differences in innovative behavior and inquisitiveness have been linked to social complexity and neocortical size [18]. In this study, we observed behavioral actions among nine socially reared and socially housed capuchin monkeys in response to an unfamiliar object, a paradigm widely employed as a means to assess curiosity.

We describe here a highly successful, de novo C-terminal sequenci

We describe here a highly successful, de novo C-terminal sequencing method of proteins by employing succinimidyloxycarbonylmethyl tris (2,4,6-trimethoxyphenyl) phosphonium bromide and mass spectrometry.”
“People reliably and automatically make personality inferences from facial appearance despite little evidence for their accuracy. Although such inferences are highly inter-correlated, research has traditionally focused on studying specific traits such AZD1080 as trustworthiness. We advocate

an alternative, data-driven approach to identify and model the structure of face evaluation. Initial findings indicate that specific trait inferences can be represented within a 2D space defined by valence/trust-worthiness and power/dominance evaluation of faces. Inferences along these dimensions are based on similarity to expressions signaling approach or avoidance behavior and features signaling physical strength, respectively, indicating that trait inferences from faces originate in functionally adaptive mechanisms. We conclude with a discussion of the potential role of the amygdala in face evaluation.”
“It is suggested that the sex steroid hormones testosterone and estrogen (SSH) provide receptor cells with reliable information on protein synthesis and on the level of oxidative metabolism selleck screening library in the cells of the gonads. The SSH are derived from the oxidation of cholesterol. This oxidation

is a side reaction of the oxidative processes in the mitochondria that generate most of the energy to the organism. The amount of SSH that is synthesized is correlated to the partial pressure of oxygen at the synthesizing cells. The amount

of free SSH that a cell can hold is checked by the damage that free steroids may cause. This damage is prevented by proteins that bind with SSH. As a result, SSH levels are correlated also with the ability of the SSH synthesizing cell to produce proteins that bind with them. A cell can 3-oxoacyl-(acyl-carrier-protein) reductase only synthesize SSH in relation to the oxidative processes within it and to its ability to produce the binding proteins necessary to prevent the damage caused by SSH. As a result, the information conveyed by SSH is reliable. We examine the specific damage caused by testosterone and estrogen, and suggest why each of them is best suited for its function. Although both SSH can provide similar information on the metabolism in the cells that synthesize them, there are secondary reasons why testosterone and estrogen were selected to serve particular functions. Testosterone improves the efficiency of the proton pump at the mitochondria in producing ATP, but increases oxidative damage. Estrogen on the other hand decreases oxygen damage but also decreases the efficiency of the proton pump. These differences between the two SSH may explain why females use estrogen to inform the body about the activity of the cells in their gonads while males do it by testosterone.

Insulin-like growth factor I (IGF-I) has been shown to increase m

Insulin-like growth factor I (IGF-I) has been shown to increase muscle mass and promote muscle cell proliferation, differentiation, and survival. We, therefore, hypothesized that IGF-I might also be cytoprotective for muscle cells during oxidative stress. Exogenous hydrogen peroxide (H(2)O(2)) was ATPase inhibitor used to induce oxidative stress/damage in two types of skeletal muscle cells. Apoptotic pathways were assessed after the oxidative damage and the effects of IGF-I on oxidative stress in muscle

cells were examined. Different IGF-I sub-pathways were analyzed with measurement of the expression of pro- and antiapoptotic proteins. It was found that H(2)O(2) diminishes muscle cell viability and induces a caspase-independent apoptotic cell death. Pretreatment with IGF-I protects muscle cells from H(2)O(2)-induced cell death and enhances muscle cells survival. This effect appears to result from the promotion of the anti-apoptotic protein, Bcl2. Further investigation shows that protection is via an IGF-I sub-pathway: PI3K/Akt and ERK1/2 MAPK pathways. Protecting muscle cells from oxidative damage presents a potential application in the treatment of the muscle wasting, which appears in many muscle pathologies including Duchenne muscle dystrophy and sarcopenia.”
“Bone selleck chemical mass is determined by bone cell

differentiation, activity, and death, which Liothyronine Sodium mainly occur through apoptosis. Apoptosis can be triggered by death receptor Fas (CD95), expressed on osteoblasts and osteoclasts and may be regulated by estrogen. We have previously shown that signaling through Fas inhibits osteoblast differentiation. In this study we analyzed Fas as a possible mediator of bone loss induced by estrogen withdrawal. At 4 weeks after ovariectomy (OVX), Fas gene expression was greater in osteoblasts and lower in osteoclasts in ovariectomized

C57BL/6J (wild type (wt)) mice compared with sham-operated animals. OVX was unable to induce bone loss in mice with a gene knockout for Fas (Fas -/- mice). The number of osteoclasts increased in wt mice after OVX, whereas it remained unchanged in Fas -/- mice. OVX induced greater stimulation of osteoblastogenesis in Fas -/- than in wt mice, with higher expression of osteoblast-specific genes. Direct effects on bone cell differentiation and apoptosis in vivo were confirmed in vitro, in which addition of estradiol decreased Fas expression and partially abrogated the apoptotic and differentiation-inhibitory effect of Fas in osteoblast lineage cells, while having no effect on Fas-induced apoptosis in osteoclast lineage cells. In conclusion, the Fas receptor has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and inhibiting differentiation of osteoblast lineage cells.