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Tim Schwarting Philipp Lechler Johannes Struewer Marius Ambrock Thomas Manfred Frangen Steffen Ruchholtz Ewgeni Ziring Michael Frink 《PloS one》2015,10(2)
IntroductionSuccessful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration.ResultsIn both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures.DiscussionThis study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts.ConclusionOur findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts at the tendon-bone interface. 相似文献
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Wayne W. Poon Anthony J. Carlos Brittany L. Aguilar Nicole C. Berchtold Crystal K. Kawano Vahe Zograbyan Tim Yaopruke Michael Shelanski Carl W. Cotman 《The Journal of biological chemistry》2013,288(23):16937-16948
We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival. 相似文献
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H B Barlow 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1980,290(1038):71-82
Our perceptions of the world around us are stable and reliable. Is this because the mechanisms that yield them are crude and insensitive and thus immune to false responses? Or is it because a statistical censor that blocks unreliable messages intervenes between the signals from our sense organs and our knowledge of them? This question can be answered by measuring the efficiency with which statistical information is utilized in perception. It is shown that mirror symmetry can be detected in displays of otherwise random dots with an efficiency of up to 50%; thus the statistical mechanisms are not crude and insensitive, and this aspect of sensory physiology and psychology may deserve more attention. 相似文献
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