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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 | Air emissions from foundries: a current survey of literature, suppliers and foundrymen 显示文摘 | McKinley M D Jefcoat I A Herz W J | 1993 | American Foundry Society Transactions1993，101，： | 1 |
| 3 | Structures and functions of multiligand lipoprotein receptor:Macrophage scavenger receptors and LDL receptor- related protein (LRP)显示文摘 | Krieger M Herz J | 1994 | Annu Rev Biochem1994，63，5： | 1 |
| 4 | Abnormal cervical cytology after al- logeneic bone marrow transplantation 显示文摘 | Negri G Herz M Deola S | 2014 | Am J Clin Pathol2014，142，2： | 1 |
| 5 | Sythesis and radiopharmacology of O- ( 2- fluorethyl )-L-tyrosine for tumor imaging显示文摘 | Wester HJ Herz M Weber W | 1999 | J Nucl Med1999，40，： | 1 |
| 6 | Acrosome reaction of bovine Spermatozoa in vivo:Sites and effects of stages of the estrous cycle 显示文摘 | Herz Z Northey D Lawyer M | 1985 | Biol Reprod1985，32，5： | 1 |
| 7 | Specificity of opioids towards the μ-, δ-, and ε-opioid receptors显示文摘 | Wuster M Schulz R Herz A | 1978 | Neuroscience Lett1978，15，： | 1 |
| 8 | Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics 显示文摘 | Kalliomaki M Antoine JM Herz U | 2010 | J Nutr2010，140，3： | 1 |
| 9 | Electrocardiographic criteria for predicting the culprit artery in inferior wall acute myocardial infarction显示文摘 | Assali AR Herz I Vaturi M | 1999 | Am J Cardiol1999，84，1： | 1 |
| 10 | Isolated oculomotor nerve palsy as the presenting clinical manifestation of a meningeal carcinomatosis: a case report显示文摘 | Nardone R Herz M | 2006 | Neurol Sci2006，27，4： | 1 |
| 11 | Guidance for substanti- ating the evidence for beneficial effects of probiotics : prevention and management of allergic diseases by probioties显示文摘 | Kalliomaki M Antoine JM Herz U | 2010 | J Nutr2010，140，3： | 1 |
| 12 | Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation,but not airway responsiveness in a murine model of experimental asthma显示文摘 | 1N Blu mer U Herz M Wegmarn | 2005 | Clin Exp Allergy2005，35，： | 1 |
| 13 | Apolipoprotein E Induces Antiinflammatory Phenotype in Macrophages显示文摘 | Daniel Baitsch Hans H. Bock Thomas Engel Ralph Telgmann Carsten Müller-Tidow Georg Varga Martine Bot Joachim Herz Horst Robenek Arnold von Eckardstein Jerzy-Roch Nofer | 2011 | Arteriosclerosis, Thrombosis, and Vascular Biology2011，，5： | 1 |
| 14 | Nonobstructive aortic valve calcification: a window to significant coronary artery disease显示文摘 | Adler Y Vaturi M Herz I | 2002 | Atherosclerosis2002，161，1： | 1 |
| 15 | Enhancer- associated H3 K4 monomethylation by Trithorax - related, the Drosophila hom- olog of mammalian Ml13/Ml14 显示文摘 | Herz HM Mohan M Garruss AS | 2012 | Genes Dev2012，26，23： | 1 |
| 16 | Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probioties 显示文摘 | Kalliomaki M Antoine JM Herz U | 2010 | JNutr2010，140，3： | 1 |
| 17 | SET for life: Bi- ochemical activities and biological functions of SET domain-containing proteins显示文摘 | Herz H M Garruss A Shilatifard A | 2013 | Trends Biochem Sci2013，38，12： | 1 |
| 18 | Electrocardiographic criteria for predicting the culprit artery in inferior wall acute myocardial infarction显示文摘 | Assali AR Herz I Vaturi M | 1999 | Am J Cardiol1999，84，： | 1 |
| 19 | Mitral annular calcium detected by transthoracic echocardiography is a marker for high prevalence and severity of coronary artery disease in patients undergoing coronary angiography显示文摘 | Adler Y Herz 1 Varuri M | 1998 | Am J Cordiol1998，82，10： | 1 |
| 20 | Guidance for sub- stantiating the evidence for beneficial effects of probiotics: Probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome 显示文摘 | Kalliomaki M Antoine JM Herz U | 2010 | J Nutr2010，140，3： | 1 |
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