1,720,999 research outputs found
Bias in bones: Integrating sex into skeletal health and research policy to improve public health
No full textPersonalised medicine has a growing role to play in improving diagnoses of conditions and providing tailored treatments. It is therefore uniquely placed to address growing skeletal health inequalities identified through this research. We have identified that preclinical laboratory experiments favour only one sex, resulting in clinical biases where drugs studied and optimised for women are also given to men. If not addressed this bias will also negatively impact the progress and effectiveness of sex specific therapies for skeletal disease. Development of sex-specific medicines and therapy for bone health should also be supported by robust research policy to avoid exacerbating these inequalities
Editorial. Achieving tissue specific levels of angiogenesis: Not(ch) a big deal!
No full textOur understanding of the molecular mechanisms regulating endothelial cell behavior in bone vs. other organs has been challenging to date given the inaccessibility of blood vessels deep within the bone mineral and the difficulties associated with bone endothelial cell isolation. A recent study published by Ramasamy et al., combined postnatal modification of endothelial cell specific Notch signals with improved immunohistochemical approaches and bone endothelial cell isolation, to highlight for the first time the presence of clear bone endothelial cell heterogeneity
Are mesenchymal stem cells so bloody great after all?
No full textThis perspective discusses some activities of mesenchymal stem cells (MSCs) in the context of angiogenesis, focusing on contrasting effects that could call into question the extent to which MSCs can be used clinically in the future. We report on the antiangiogenic/antiproliferative effects of specific MSC populations (including bone marrow MSCs), their paracrine activity, tissue heterogeneity, and endothelial cell interactions. Also discussed are what could lead to contrasting effects of the influence of MSCs in regulating angiogenesis, pointing to some negative effects of these cells. In conclusion, this article highlights important aspects of MSC behavior within the perspective of translational medicine applications.SignificanceMultipotent mesenchymal stem cells (MSCs) can be extracted from virtually every organ and tissue in the body. Although they have previously been shown to be an important source of blood vessel-attracting factors, useful for tissue repair and regenerative medicine, recent studies have found that specific MSC populations can also produce factors that inhibit blood vessel growth. Abnormal vascularization is associated with the progression of many diseases, and identification of these unique blood vessel-inhibiting MSCs has highlighted a potential source of cytotoxic factors that could be used to control pathological angiogenesis, for example, tumor
Datasets for Doctoral Thesis "Of mice and women: Utilising high-resolution computed tomography for extrapolation of murine and human sexual dimorphism in cortical bone microstructure and fracture risk"
No full textDataset to support University of Southampton doctoral thesis, "Of mice and women: Utilising high-resolution computed tomography for extrapolation of murine and human sexual dimorphism in cortical bone microstructure and fracture risk"
Preclinical data on pre-pubertal and post-pubertal wildtype mice, four-core genotype mice, and mechanically loaded mice.
Clinical data on recruits during 44 weeks of military training.</span
Commentary: A cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cells
No full textA Commentary onA cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cellsby Buo, A. M., Williams, M. S., Kerr, J. P., and Stains, J. P. (2016). Bone Res. 4:16021. doi: 10.1038/boneres.2016.2
On bone-forming cells and blood vessels in bone development
No full textReplacement of nonvascular cartilage by bone and bone marrow is a critical step in bone development. In a recent issue of Developmental Cell, Maes et al. (2010) report that a distinct population of immature precursors of bone-forming cells migrate into the cartilage in intimate association with invading blood vessels
Dataset in support of the thesis 'Harnessing label-free, non-linear microscopy for research and diagnosis of osteosarcoma'
No full textData associated with my doctoral thesis. More specifically, collagen fibre parameters extracted from second harmonic generation images of clinical bone and osteosarcoma biopsies. </span
Bias in bones: integrating sex into skeletal health and research policy to improve public health outcomes
Full text linkOsteoporotic fractures are a major public health concern. Fragility fractures result in serious disability, impacting quality of life, and mortality risk. Understanding fractures is important for creating successful interventions to reduce fracture risk and improve the delivery of skeletal health care. Further, as the population ages the increasing prevalence of fragility fractures is a growing economic issue.It is well understood that women and men have anatomically and physiologically different bone structures. With age, women have a higher incidence of fragility fractures than men but men are twice as likely to die following an osteoporotic-fracture. Gender influence is also evident in other skeletal conditions including osteopenia, Paget’s disease of bone, osteoarthritis and osteosarcoma. In the UK, there have been several attempts to shift from population to individual based therapeutic approaches. The aim would be to have more personalised treatments that would provide more effective treatment options for women and men.However, the translation of personalised medicines from laboratories to the clinic is challenged at pre-clinical stage by historic sex bias, whereby laboratories favour one sex for their experiments. This bias translates to clinics where drugs studied and optimised for women with osteoporosis for example are given to men
Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: a negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?
No full textIn bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE(2) on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure of ECs to PGE(2) increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF(1alpha) release and EC proliferation. In contrast, PGE(2) attenuated VEGF(165)-induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE(2) restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH(2) (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling
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