In utero substrate restriction by placental insufficiency or maternal undernutrition decreases optical redox ratio in foetal perirenal fat

Intrauterine growth restriction (IUGR) can result from reduced delivery of substrates, including oxygen and glucose, during pregnancy and may be caused by either placental insufficiency or maternal undernutrition. As a consequence of IUGR, there is altered programming of adipose tissue and this can be associated with metabolic diseases later in life. We have utilised two sheep models of IUGR, placental restriction and late gestation undernutrition, to determine the metabolic effects of growth restriction on foetal perirenal adipose tissue (PAT). Two-photon microscopy was employed to obtain an optical redox ratio, which gives an indication of cell metabolism. PAT of IUGR foetuses exhibited higher metabolic activity, altered lipid droplet morphology, upregulation of cytochrome c oxidase subunit genes and decreased expression of genes involved in growth and differentiation. Our results indicate that there are adaptations in PAT of IUGR foetuses that might be protective and ensure survival in response to an IUGR insult.     

Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin

p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53^+/+, p53^+/−, and p53^−/− mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling.Subject terms: Cell biology, Pathogenesis     

Regulation of osteoblast and osteoclast functions by FGF‐6

Fibroblast growth factor‐6 (FGF‐6) is known to be the key ligand for fibroblast growth factor receptor 4 (FGFR4) during muscle regeneration but its role in bone has yet to be verified. FGFR signaling is known to be important in the initiation and regulation of osteogenesis, so in this study the actions of FGF‐6 on human osteoblasts and osteoclasts were investigated. Human primary osteoblasts (hOB) were used to study the effect of FGF‐6 on proliferation (by ATP quantification), signal transduction (by ERK and AKT phosphorylation), differentiation (by alkaline phosphatase activity, APA), and mineralization (by calcein staining). To study FGF‐6 activity on osteoclast differentiation, human bone marrow cells were used and tartrate‐resistant acid phosphatase (TRAP) multinucleated cells together with actin filaments arrangements were quantified. Human primary mature osteoclasts were used to evaluate the effect of FGF‐6 on osteoclast reabsorbing activity by reabsorbed pit measurements. FGF‐6 >10⁻⁹ M as FGF‐2 10⁻⁷ M induced hOB proliferation mediated by pERK together with a reduction in APA and reduced mineralization of the treated cells. Moreover FGF‐6 increased the formation of TRAP‐positive multinucleated cells in a dose‐dependent manner (maximal effect at 10⁻⁸ M). FGF‐6‐treated cells showed also a greater percentage of cells that formed typical osteoclast sealing zones. Mature osteoclasts cultured on dentine slice increased the area of reabsorption with a maximal effect of FGF‐6 at 10⁻¹² M. FGF‐6 may be considered a regulator of bone metabolism as shown by its activity on both osteoblasts and osteoclasts. J. Cell. Physiol. 225: 466–471, 2010. © 2010 Wiley‐Liss, Inc.     

Release Properties of Hydrogels: Water Evaporation from Alginate Gel Beads

Encapsulation in alginate hydrogels has been extensively used for several applications in food, pharmaceutical, and biomedical fields. The rational design of a functional polymer network is based on the identification of key parameters and mechanisms governing rate and extent of release of the immobilized molecular species. In the present work, a calorimetric study of the water evaporation under non-isothermal conditions is aimed at evaluating functional properties of a series of alginate-based gel beads. The experiments show how a number of variables, such as scan rate, calcium and alginate concentration, operational procedures, and addition of biopolymer co-solutes influence the temperature evolution of the water evaporation from beads. Given the simplicity and the rapidity of the calorimetric experiment, the issue is raised that a scaling approach could be reached by using water as reference material for the prediction of the diffusion kinetics of encapsulated molecules of variable size and properties.     

Shedding light on auxin movement: Light-regulation of polar auxin transport in the photocontrol of plant development

By being sessile, plants have evolved a remarkable capacity to perceive and respond to changes in environmental conditions throughout their life cycle. Light represents probably the most important environmental factor that impinge on plant development because, other than supplying the energy source for photosynthesis, it also provides seasonal and positional information that are essential for the plant survival and fitness. Changes in the light environment can dramatically alter plant morphogenesis, especially during the early phases of plant life, and a compelling amount of evidence indicates that light-mediated changes in auxin homeostasis are central in these processes. Auxin exerts its morphogenetic action through instructive hormone gradients that drive developmental programs of plants. Such gradients are formed and maintained via an accurate control on directional auxin transport. This review summarizes the recent advances in understanding the influence of the light environment on polar auxin transport.