|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 3 | A vital sugar code for ricin toxicity显示文摘 | Jasmin Taubenschmld Johannes Stadlmann Markus Jost Tove Irene Klok.k Cory D Rillahan Andreas Leibbrandt Karl Mechtler James C Paulson Julian Jude Johannes Zuber Kirsten Sandvig Ulrich Elling Thorsten Marquardt Christian Thiel Christian Koerner Josef M Penninger | 2017 | Cell Research2017，27，11： | 2 |
| 4 | Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients显示文摘 | Martin A. Burschka Hassan Abdel-Hady Hassan Thorsten Reineke Lara van Bebber David M. Caird R. M?sges | 2001 | European Archives of Oto - Rhino - Laryngology2001，，5： | 1 |
| 5 | Puff-by-puff resolved characterization of cigarette mainstream smoke by single photon ionization (SPI)-time-of-flight mass spectrometry (TOFMS): Comparison of the 2R4F research cigarette and pure Burley, Virginia, Oriental and Maryland tobacco cigarettes显示文摘 | THOMAS A STEFAN M THORSTEN S | 2006 | Analytica Chimica Acta2006，572，2： | 1 |
| 6 | L1 Is Sequentially Processed by Two Differently Activated Metalloproteases and Presenilin/γ -Sretase and Regulates Neural Cell Adhesion, Cell Migration, and Neurite Outgrowth 显示文摘 | Thorsten M | 2005 | Molecular & Cellular Biology2005，25，20： | 1 |
| 7 | Two models of endothelial dysfunction:the importance of intrinsic cardioprotective properties of the coronary-endothelium 显示文摘 | THORSTEN M LEUCKER GE ZHI-DONG JESSE PRO- CKNOW | 2013 | Arterioscler Thromb Vasc Biol2013，33，5： | 1 |
| 8 | Disabling low back pain and depressive symptoms in the community-dwelling elderly显示文摘 | Thorsten M James C Heiner R | 2007 | Spine2007，32，21： | 1 |
| 9 | Electronic Brake Control for Greater Active Safety 显示文摘 | Bernhard Eichhorn M Steffen Ktnig Thorsten Ullrich | 2014 | ATZ worldwide2014，116，9： | 1 |
| 10 | Brain and heart-type fatty acid-binding proteins in the brain:tissue distrbution and clinical utility显示文摘 | Maurice M Thorsten H Danielle vander V | 2004 | Clinical Chemistry2004，50，9： | 1 |
| 11 | Financial Intermediary Development and Growth Volatility:Do Intermediaries Dampen Ormagnify Shocks?显示文摘 | THORSTEN B MATTIAS L GIOVANNI M | 2006 | Journal of International Money and Finance2006，25，： | 1 |
| 12 | Bonding Characteristics of a New Type of Prestressing Steel Wire with Spiral Ribbing 显示文摘 | THORSTEN S FALK M | 2008 | Reinforcement Technology2008，，2： | 1 |
| 13 | Disabling low back pain and depressive symptoms in the community-dwelling elderly显示文摘 | Thorsten M James C Heiner R | 2007 | Spine2007，32，21： | 1 |
| 14 | Financial intermediary development and growth volatility: Do intermediaries dampen or magnify shocks? 显示文摘 | Thorsten B Mattias L Giovanni M | 2006 | Journal of International Money and Finance2006，25，： | 1 |
| 15 | Gluc- Lys (FP)-TOCA PET in Patients With SSTR- Positive Tumors: Biodistribution and Diagnostic Evaluation Compared With DTPA-Octreotide显示文摘 | Gianther M Thorsten P Alexander S | 2006 | J Nucl Med2006，47，： | 1 |
| 16 | Cell tagging with clinically approved iron oxides:feasibility and effect of lipofection,particle size,and surface coating on labeling efficiency显示文摘 | Lars M Thorsten P Alexander W | 2005 | Radiology2005，235，1： | 1 |
| 17 | Thermal desorption/pyrolysis coupled with photoionization time-of-flight mass spectrometry for the analysis of molecular organic compounds and oligomerie and polymeric fractions in urban particulate matter 显示文摘 | Thorsten S Jochen W Stefan M | 2006 | Anal Chem2006，78，： | 1 |
| 18 | 1,8-cineol inhibits nuclear translocation of NF-κB p65 and NF-κB-dependent transcriptional activity显示文摘 | Johannes F.-W. Greiner Janine Müller Marie-Theres Zeuner Stefan Hauser Thorsten Seidel Christin Klenke Lena-Marie Grunwald Timo Schomann Darius Widera Holger Sudhoff Barbara Kaltschmidt Christian Kaltschmidt | 2013 | BBA - Molecular Cell Research2013，，： | 1 |
| 19 | The effect of steroids in combina- tion with optic nerve decompression surgery in traumatic optic neuropathy显示文摘 | Thorsten R Bernhard S Cem M | 2013 | Laryngoscope2013，123，5： | 1 |
| 20 | Total hip arthroplasties: What are the reasons for revision显示文摘 | Slif D Thorsten M Ronald E | 2008 | International Orthopaedics2008，32，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员