{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670320863169408.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1359/jbmr.081006"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1359%2Fjbmr.081006"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jbmr/article/24/2/241/7599864"}},{"identifier":{"@type":"PMID","@value":"18847324"}}],"dc:title":[{"@value":"Activation of Renin-Angiotensin System Induces Osteoporosis Independently of Hypertension"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n               <jats:p>Hypertension and osteoporosis are two major age-related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin-angiotensin system (RAS) plays a central role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, we showed in this study that activation of RAS induces high turnover osteoporosis with accelerated bone resorption. Transgenic mice that express only the human renin gene were normotensive and yet exhibited a low bone mass, suggesting that osteoporosis occurs independently of the development of hypertension per se. Ex vivo cultures showed that angiotensin II (AngII) acted on osteoblasts and not directly on osteoclast precursor cells and increased osteoclastogenesis-supporting cytokines, RANKL and vascular endothelial growth factor (VEGF), thereby stimulating the formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor paradoxically enhanced it, suggesting a functional interaction between the two AngII receptors on the osteoblastic cell surface. Finally, treatment of THM mice with an ACE inhibitor, enalapril, improved osteoporosis and hypertension, whereas treatment with losartan, an angiotensin receptor blockers specific for AT1, resulted in exacerbation of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis and hypertension, especially for those afflicted with both conditions.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670320863169417","@type":"Researcher","foaf:name":[{"@value":"Yutaro Asaba"}],"jpcoar:affiliationName":[{"@value":"Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"},{"@value":"Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169409","@type":"Researcher","foaf:name":[{"@value":"Masako Ito"}],"jpcoar:affiliationName":[{"@value":"Department of Radiology, Nagasaki University School of Medicine, Nagasaki, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169414","@type":"Researcher","foaf:name":[{"@value":"Toshio Fumoto"}],"jpcoar:affiliationName":[{"@value":"Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169408","@type":"Researcher","foaf:name":[{"@value":"Ken Watanabe"}],"jpcoar:affiliationName":[{"@value":"Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169411","@type":"Researcher","foaf:name":[{"@value":"Ryoji Fukuhara"}],"jpcoar:affiliationName":[{"@value":"Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169410","@type":"Researcher","foaf:name":[{"@value":"Sunao Takeshita"}],"jpcoar:affiliationName":[{"@value":"Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169416","@type":"Researcher","foaf:name":[{"@value":"Yuji Nimura"}],"jpcoar:affiliationName":[{"@value":"Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169413","@type":"Researcher","foaf:name":[{"@value":"Junji Ishida"}],"jpcoar:affiliationName":[{"@value":"Life Sciences and Bioengineering, Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169415","@type":"Researcher","foaf:name":[{"@value":"Akiyoshi Fukamizu"}],"jpcoar:affiliationName":[{"@value":"Aspect of Functional Genomic Biology, Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki, Japan"},{"@value":"Life Sciences and Bioengineering, Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320863169412","@type":"Researcher","foaf:name":[{"@value":"Kyoji Ikeda"}],"jpcoar:affiliationName":[{"@value":"Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"08840431"},{"@type":"EISSN","@value":"15234681"}],"prism:publicationName":[{"@value":"Journal of Bone and Mineral Research"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2009-02-01","prism:volume":"24","prism:number":"2","prism:startingPage":"241","prism:endingPage":"250"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1359%2Fjbmr.081006"},{"@id":"https://academic.oup.com/jbmr/article/24/2/241/7599864"}],"createdAt":"2008-10-10","modifiedAt":"2024-03-13","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Vascular%20Endothelial%20Growth%20Factor%20A","dc:title":"Vascular Endothelial Growth Factor A"},{"@id":"https://cir.nii.ac.jp/all?q=Osteoblasts","dc:title":"Osteoblasts"},{"@id":"https://cir.nii.ac.jp/all?q=Angiotensin%20II","dc:title":"Angiotensin II"},{"@id":"https://cir.nii.ac.jp/all?q=RANK%20Ligand","dc:title":"RANK Ligand"},{"@id":"https://cir.nii.ac.jp/all?q=Angiotensinogen","dc:title":"Angiotensinogen"},{"@id":"https://cir.nii.ac.jp/all?q=Angiotensin-Converting%20Enzyme%20Inhibitors","dc:title":"Angiotensin-Converting Enzyme Inhibitors"},{"@id":"https://cir.nii.ac.jp/all?q=Angiotensin%20II%20Type%202%20Receptor%20Blockers","dc:title":"Angiotensin II Type 2 Receptor Blockers"},{"@id":"https://cir.nii.ac.jp/all?q=Receptor,%20Angiotensin,%20Type%202","dc:title":"Receptor, Angiotensin, Type 2"},{"@id":"https://cir.nii.ac.jp/all?q=Receptor,%20Angiotensin,%20Type%201","dc:title":"Receptor, Angiotensin, Type 1"},{"@id":"https://cir.nii.ac.jp/all?q=Renin-Angiotensin%20System","dc:title":"Renin-Angiotensin System"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Hypertension","dc:title":"Hypertension"},{"@id":"https://cir.nii.ac.jp/all?q=Renin","dc:title":"Renin"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Osteoporosis","dc:title":"Osteoporosis"},{"@id":"https://cir.nii.ac.jp/all?q=Bone%20Remodeling","dc:title":"Bone Remodeling"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232001001472","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mineralocorticoid receptor function in bone metabolism and its role in glucocorticoid-induced osteopenia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360025431113899264","@type":"Article","resourceType":"学術雑誌論文(journal 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