1,133 research outputs found

    Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

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    Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages

    Surface-Initiated Polymer Brushes in the Biomedical Field: Applications in Membrane Science, Biosensing, Cell Culture, Regenerative Medicine and Antibacterial Coatings

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    AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model

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    <p>Abstract</p> <p>Background</p> <p>Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression <it>in vivo</it>. The objective of this work was to evaluate the ability of AAV-mediated human PEDF (hPEDF) as a potent tumor suppressor and a potential candidate for cancer gene therapy.</p> <p>Methods</p> <p>Recombinant AAV<sub>2 </sub>encoding hPEDF (rAAV<sub>2</sub>-hPEDF) was constructed and produced, and then was assigned for <it>in vitro </it>and <it>in vivo </it>experiments. Conditioned medium from cells infected with rAAV<sub>2</sub>-hPEDF was used for cell proliferation and tube formation tests of human umbilical vein endothelial cells (HUVECs). Subsequently, colorectal peritoneal carcinomatosis (CRPC) mouse model was established and treated with rAAV<sub>2</sub>-hPEDF. Therapeutic efficacy of rAAV<sub>2</sub>-hPEDF were investigated, including tumor growth and metastasis, survival time, microvessel density (MVD) and apoptosis index of tumor tissues, and hPEDF levels in serum and ascites.</p> <p>Results</p> <p>rAAV<sub>2</sub>-hPEDF was successfully constructed, and transmission electron microscope (TEM) showed that rAAV<sub>2</sub>-hPEDF particles were non-enveloped icosahedral shape with a diameter of approximately 20 nm. rAAV<sub>2</sub>-hPEDF-infected cells expressed hPEDF protein, and the conditioned medium from infected cells inhibited proliferation and tube-formation of HUVECs <it>in vitro</it>. Furthermore, in CRPC mouse model, rAAV<sub>2</sub>-hPEDF significantly suppressed tumor growth and metastasis, and prolonged survival time of treated mice. Immunofluorescence studies indicated that rAAV<sub>2</sub>-hPEDF could inhibit angiogenesis and induce apoptosis in tumor tissues. Besides, hPEDF levels in serum and ascites of rAAV<sub>2</sub>-hPEDF-treated mice were significant higher than those in rAAV<sub>2</sub>-null or normal saline (NS) groups.</p> <p>Conclusions</p> <p>Thus, our results suggest that rAAV<sub>2</sub>-hPEDF may be a potential candidate as an antiangiogenic therapy agent.</p

    Observation of Charge-Dependent Azimuthal Correlations in p-Pb Collisions and Its Implication for the Search for the Chiral Magnetic Effect

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    Cross section measurement of t-channel single top quark production in pp collisions at root s=13 TeV

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    Search for narrow resonances in dilepton mass spectra in proton-proton collisions at root s=13 TeV and combination with 8 TeV data

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    Measurement of the production cross section of a W boson in association with two b jets in pp collisions at root s=8TeV

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    Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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    Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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    Search for top squark pair production in pp collisions at root s=13 TeV using single lepton events

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