Ras signaling regulates osteoprogenitor cell proliferation and bone formation

During endochondral bone development, osteoblasts are continuously differentiated from locally residing progenitor cells. However, the regulation of such endogenous osteoprogenitor cells is still poorly understood mainly due to the difficulty in identifying such cells in vivo. In this paper, we genetically labeled different cell populations of the osteoblast linage using stage-specific, tamoxifen-inducible Cre transgenic mice to investigate their responses to a proliferative stimulus. We have found that overactivation of Kras signaling in type II collagen-positive, immature osteoprogenitor cells, but not in mature osteoblasts, substantially increases the number of their descendant stromal cells and mature osteoblasts, and subsequently increases bone mass. This effect was mediated by both, the extracellular signal-regulated kinase (ERK) and phosphoinositide 3 kinase (PI3K), pathways. Thus we demonstrate that Ras signaling stimulates proliferation of immature osteoprogenitor cells to increase the number of their osteoblastic descendants in a cell-autonomous fashion

Determinants of developing diabetes mellitus and vascular complications in patients with impaired fasting glucose

Aims: To detect the risk factors of diabetes mellitus (DM) and cardiovascular complications in subjects with impaired fasting glucose (IFG). Materials and Methods: One hundred and twenty three subjects with proved IFG in Zanjan Healthy Heart Study (2002-2003) were recalled and participated in this study (2009-2010). Demographic and laboratoryinformation of the participants were collected.Ischemic heart disease (IHD) was assessed by the exercise tolerance test (ETT). All the subjects with abnormal ETT or documented past history of IHD confirmed by angiographic evaluation. Ophthalmic complications including cataract, glaucoma, and diabetic retinopathy were estimated by an ophthalmologist. Results: Incidence of DM was 19.5%. All the diabetic and pre-diabetic patients had at least one of the other components of metabolic syndrome. Obesity (P: 0.04, OR: 1.8, 95%CI: 1.2-9) and low physical activity (P < 0.001, OR: 9.6, 95%CI: 3.4-32) were the only independent prognostic risk factors for progression to DM in patients with IFG. Total incidence of IHD was 14.6% and had a strong correlation with sex (P: 0.01, OR: 1.8, 95%CI: 1.2-1.5), age (P < 0.001, OR: 23, 95%CI: 2.1-67) and cigarette smoking (P < 0.001, OR: 36.5, 95%CI: 3.9-337). Non-proliferative diabetic retinopathy was shown in 2 (1.6%) subjects who were all women. Conclusion: Obesity and low physical activity are the main factors of developing DM and its macrovascular complications in subjects with IFG

Distinct molecular pathways mediate Mycn and Myc-regulated miR-17-92 microRNA action in Feingold syndrome mouse models

Feingold syndrome is a skeletal dysplasia caused by loss-of-function mutations of either MYCN (type 1) or MIR17HG that encodes miR-17-92 microRNAs (type 2). Since miR-17-92 expression is transcriptionally regulated by MYC transcription factors, it has been postulated that Feingold syndrome type 1 and 2 may be caused by a common molecular mechanism. Here we show that Mir17-92 deficiency upregulates TGF-β signaling, whereas Mycn-deficiency downregulates PI3K signaling in limb mesenchymal cells. Genetic or pharmacological inhibition of TGF-β signaling efficiently rescues the skeletal defects caused by Mir17-92 deficiency, suggesting that upregulation of TGF-β signaling is responsible for the skeletal defect of Feingold syndrome type 2. By contrast, the skeletal phenotype of Mycn-deficiency is partially rescued by Pten heterozygosity, but not by TGF-β inhibition. These results strongly suggest that despite the phenotypical similarity, distinct molecular mechanisms underlie the pathoetiology for Feingold syndrome type 1 and 2

The Effects of Unripe Grape Juice on Lipid Profile Improvement

Introduction. Consumption of unripe grape juice (verjuice) has been portrayed by the traditional belief, as a means of combating dyslipidemia. We aimed to evaluate the effects of unripe grape juice consumption on lipid profile in healthy human volunteers. Methods. We asked 42 enrolled volunteers to drink 10 cc of verjuice within 30 minutes to 2 hours after lunch and 10 cc of it after dinner. After taking 120 doses of verjuice, another fasting lipid profile was obtained from each participant. The statistical analysis was performed by SPSS 13 software. Results. After analysis of the data, the mean ± standard deviation for all the variables was obtained. Among those improvement of HDL-C was significant after the trial (value<0.001). TG, TC, and LDL improvement were not significant. Conclusion. Our study declared that verjuice has a dramatic effect on improving HDL-C level of serum but no any other lipid improvement effect was obtained

Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling

Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in chondrocytes causes severe kyphosis and a growth defect with decreased chondrocyte proliferation, accelerated hypertrophic differentiation and cell death with reduced Hif1a expression. Eed deficiency also causes induction of multiple signalling pathways in chondrocytes. Wnt signalling overactivation is responsible for the accelerated hypertrophic differentiation and kyphosis, whereas the overactivation of TGF-β signalling is responsible for the reduced proliferation and growth defect. Thus, our study demonstrates that PRC2 has an important regulatory role in lineage-committed tissue cells by suppressing overactivation of multiple signalling pathways