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| 1 | Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling显示文摘Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1(Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass.Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand(RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor(PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRβ-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF–RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans. | Alexander Bartelt Friederike Behler-Janbeck F.Timo Beil Till Koehne Brigitte Müller Tobias Schmidt Markus Heine Laura Ochs Tayfun Yilmaz Martin Dietrich Jan P.Tuckermann Michael Amling Joachim Herz Thorsten Schinke Joerg Heeren Andreas Niemeier | 2018 | Bone Research2018，6，1： | 5 |
| 2 | Radioembolization with yttrium‐90 glass microspheres in hepatocellular carcinoma: European experience on safety and long‐term survival显示文摘 | Philip Hilgard Monia Hamami Amr El Fouly André Scherag Stefan Müller Judith Ertle Till Heusner Vito R. Cicinnati Andreas Paul Andreas Bockisch Guido Gerken Gerald Antoch | 2010 | Hepatology2010，，： | 3 |
| 3 | Endoscopic findings in patients with Schatzki rings:Evidence for an association with eosinophilic esophagitis显示文摘AIM:To investigate endoscopic findings in patients with Schatzki rings(SRs) with a focus on evidence for eosinophilic esophagitis(EoE).METHODS:We consecutively approached all adult patients scheduled for elective outpatient upper endoscopy for a variety of indications at the German Diagnostic Clinic,Wiesbaden,Germany between July 2007 and July 2010.All patients with endoscopically diagnosed SRs,defined as thin,symmetrical,mucosal structures located at the esophagogastric junction,were prospectively registered.Additional endoscopic findings,clinical information and histopathological findings with a focus on esophageal eosinophilia(≥ 20 eosinophils/high power field) were recorded.The criteria for active EoE were defined as:(1) eosinophilic tissue infiltration ≥ 20 eosinophils/hpf;(2) symptoms of esophageal dysfunction;and(3) exclusion of other causes of esophageal eosinophilia.Gastroesophageal reflux disease was excluded by proton pump inhibitor treatment prior to endoscopy.The presence of ≥ 20 eosinophils/hpf in esophageal biopsies in patients that did not fulfil the criteria of EoE was defined as esophageal hypereosinophilia.RESULTS:A SR was diagnosed in 171(3.3%;128 males,43 females,mean age 66 ± 12.9 years) of the 5163 patients that underwent upper gastrointestinalendoscopy.Twenty of the 116 patients(17%) from whom esophageal biopsies were obtained showed histological hypereosinophilia(≥ 20 eosinophils/hpf).Nine of these patients(8 males,1 female,mean age 49 ± 10 years) did not fulfill all diagnostic criteria of EoE,whereas in 11(9%) patients with ≥ 20 eosinophils/hpf,a definite diagnosis of EoE was made.Three of the 11 patients(27%) with definite EoE had no suspicious endoscopic features of EoE.In contrast,in the 25 patients in whom EoE was suspected by endoscopic features,EoE was only confirmed in 7(28%) patients.Patients with EoE were younger(mean age 41.5 ± 6.5 vs 50.5 ± 11.5 years,P = 0.012),were more likely to have a history of allergies(73% vs 29%,P = 0.007) and complained more often of dysphagia(91% vs 34%,P = 0.004) and food impaction(36% vs 6%,P = 0.007) than patients without EoE.Endoscopically,additional webs were found significantly more often in patients with EoE than in patients without EoE(36% vs 11%,P = 0.04).Furthermore,the SR had a tendency to be narrower in patients with EoE than in those without EoE(36% vs 18%,P = 0.22).The percentage of males(73% vs 72%,P = 1.0) and frequency of heartburn(27% vs 27%,P = 1.0) were not significantly different in both groups.The 9 patients with esophageal hypereosinophilia that did not fulfil the diagnostic criteria of EoE were younger(mean age 49 ± 10 years vs 58 ± 6 years,P = 0.0008) and were more likely to have a history of allergies(78% vs 24%,P = 0.003) than patients with < 20 eosinophils/hpf.Predictors of EoE were younger age,presence of dysphagia or food impaction and a history of allergies.CONCLUSION:A significant proportion of patients with SRs also have EoE,which may not always be suspected according to other endoscopic features. | Michaela Müller Alexander J Eckardt Annette Fisseler-Eckhoff Susanne Haas Ines Gockel Till Wehrmann | 2012 | World Journal of Gastroenterology2012，18，47： | 2 |
| 4 | CD133 expression is not restricted to stem cells, and both CD133^sup +^ and CD133^sup -^ metastatic colon cancer cells initiate tumors显示文摘 | Shmelkov Sergey V Butler Jason M Hooper Andrea T Hormigo Adilia Kushner Jared Milde Till Clair Ryan St Baljevic Muhamed White Ian Jin David K Chadburn Amy Murphy Andrew J Valenzuela David M Gale Nicholas W Thurston Gavin Yancopoulos George | 2008 | Journal of Clinical Investigation2008，，： | 2 |
| 5 | comparison of different transformation for Aspergillus giganteus显示文摘 | Vera M Dirk M Till S | 2003 | Curr Genet2003，43，： | 1 |
| 6 | The nueleotide- binding oligomerization domaln-like receptor NLRC5 is in- volved in IFN-dependent antiviral immune responses 显示文摘 | KUENZEL S TILL A WINKLER M | 2010 | Journal of Immunology2010，，184： | 1 |
| 7 | Commodity Spot Prices: An Exploratory Assessment显示文摘 | SLADE M E TILLE H | 2006 | Economica2006，73，290： | 1 |
| 8 | Structural and functional integrity of precision-cut liver slices in xenobiotic metabolism:a comparison of the dynamic organ and multiwell plate culture procedures显示文摘 | Hashemi E Dobrta M Till C | 1999 | Xenobiotica1999，29，： | 1 |
| 9 | The chemokine receptor CCR7 and -4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes显示文摘 | Till KJ Lin K Zuzel M | 2002 | Blood2002，99，： | 1 |
| 10 | HDL induces NO- dependent vasorelaxation via the lysophospholipid receptor Sl P3显示文摘 | Nofer JR van der Giet M Tille M | 2004 | J Clin Invest2004，113，4： | 1 |
| 11 | Matching Products with Endorsers:Attractiveness versus Expertise显示文摘 | TILL B D BUSLER M | 1998 | Journal of Consumer Marketing1998，5，6： | 1 |
| 12 | The Match-up Hypothesis:Physical Attractiveness, Expertise, and the Role of Fit on Brand Attitude, Purchase Intent and Brand Beliefs 显示文摘 | TILL B D BUSLER M | 2000 | Journal of Advertising2000，9，3： | 1 |
| 13 | Falls as a complication of diabetes mellitus in older people显示文摘 | LINDSEY M TILLING T K HALED D | 2006 | J Diabetes Complications2006，20，： | 1 |
| 14 | Matching Products with Endorsers : Attractiveness versus Expertise 显示文摘 | Till B D Busler M | 1998 | Journal of Consumer Marketing1998，15，6： | 1 |
| 15 | Classical conditioning and celebrity endorsers: An examination of belongingness and resistance to extinction显示文摘 | Till B D Stanley S M Priluck R | 2008 | Psychology and Marketing2008，25，2： | 1 |
| 16 | The nucleotide- binding oligomerization domain-like receptor NLRC5 is in- volved in IFN-dependent antiviral immune responses 显示文摘 | KUENZEL S TILL A WINKLER M | 2010 | Journal of Immunology2010，184，4： | 1 |
| 17 | Involvement of the VEGF receptor 3 in tubularmorphogenesis demonstrated with a human antihuman VEGFR-3 monoclonal antibody that antagonizes receptor activation by VEGF-C 显示文摘 | Persaud K Tille JC Liu M | 2004 | Cell Sci2004，117，13： | 1 |
| 18 | IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA显示文摘 | Calfon M Zeng H.Q Urano F Till J.H Hubbard S.R Harding H.P Clark S.G and Ron D | | 0，，： | 1 |
| 19 | The match-up hypothesis: Physical attrac- tiveness, expertise, and the role of fit on brand attitude, purchase intent and brand beliefs显示文摘 | Till B D Busier M | 2000 | Journal of Advertising2000，19，3： | 1 |
| 20 | The great retrenchment: international capital flows during the global financial crisis显示文摘 | Milesi-Ferretti G M Tille C | 2011 | Economic Policy2011，26，66： | 1 |
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