Endoglin moves and shapes endothelial cells

Vascular malformations result from improper blood vessel responses to molecular and mechanical signals. Two studies now show that endothelial cell migration and cell shape changes are perturbed in mutants lacking the TGFβ/BMP co-receptor endoglin, leading to arteriovenous shunts. Endoglin coordinates endothelial cell responses to ligand-receptor signalling and flow-mediated mechanical cues

Impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: To investigate the impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis by conducting a systematic review of randomized controlled trials (RCTs).METHODS: Literature search up to September 2017 in five major databases with no restriction on publication year or language. Data were extracted from the first available follow-up time point and we performed a narrative synthesis for the effect of exercise therapy on molecular biomarkers related to cartilage and inflammation. A subset of studies reporting sufficient data was combined in a meta-analysis, using an adjusted random effects model.RESULTS: Twelve RCTs, involving 57 study comparisons at 4 to 24 weeks following an exercise therapy intervention were included. Exercise therapy decreased molecular biomarkers in 17 (30%) study comparisons, had no effect in 36 (63%), and increased molecular biomarkers in four (7%) study comparisons. Meta-analyses of nine biomarkers showed that exercise therapy was associated with non-significant reductions of C-reactive protein, C-terminal crosslinking telopeptide of type II collagen, tumor necrosis factor alpha (TNF-α), soluble TNF-α receptor-1 and -2, C2C neoepitope of type II collagen and cartilage oligomeric matrix protein compared to non-exercising control groups and had no effect on interleukin-6 and soluble interleukin 6 receptor.CONCLUSIONS: Exercise therapy is not harmful, as it does not increase the concentration of molecular biomarkers related to cartilage turnover and inflammation, implicated in osteoarthritis progression. The overall quality of evidence was downgraded to low because of the limited number of RCTs available. This article is protected by copyright. All rights reserved

Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6

Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation

Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases

Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases