{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:50:24Z","timestamp":1792018224502,"version":"4.4.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bone mineralization is a normal physiological process, whereas ectopic calcification of soft tissues is a pathological process that leads to irreversible tissue damage. We have established a coxsackievirus B3 (CVB3)\u2013infected mouse model that manifests both osteoporosis and ectopic calcification specifically in heart, pancreas, and lung. The CVB3-infected mice showed increased serum concentrations of both cytokines including IL-1\u03b2, TNF-\u03b1, and the receptor activator of NF-\u03baB ligand (RANKL) that stimulate osteoclast formation and of the osteoclast-derived protein tartrate-resistant acid phosphatase 5b. They exhibited more osteoclasts in bone, with no change in the number of osteoblasts, and a decrease in bone formation and the serum concentration of osteoblast-produced osteocalcin. These results indicate that CVB3-induced osteoporosis is likely due to upregulation of osteoclast formation and function, in addition to decreased osteoblast activity. In addition, the serum in the CVB3-infected mice contained a high inorganic phosphate content, which causes ectopic calcification. RANKL treatment induced an increase in the in vitro cardiac fibroblast calcification by inorganic phosphate via the upregulation of osteogenic BMP2, SPARC, Runx2, Fra-1, and NF-\u03baB signaling. We finally observed that i.p. administration of RANK-Fc, a recombinant antagonist of RANKL, prevented bone loss as well as ectopic calcification in CVB3-infected mice. Thus, our results indicate that RANKL may contribute to both abnormal calcium deposition in soft tissues and calcium depletion in bone. In addition, our animal model should provide a tool for the development of new therapeutic agents for calcium disturbance in soft and hard tissues.<\/jats:p>","DOI":"10.4049\/jimmunol.1201479","type":"journal-article","created":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T16:40:55Z","timestamp":1357836055000},"page":"1623-1630","source":"Crossref","is-referenced-by-count":12,"title":["Targeting of the Osteoclastogenic RANKL\u2013RANK Axis Prevents Osteoporotic Bone Loss and Soft Tissue Calcification in Coxsackievirus B3\u2013Infected Mice"],"prefix":"10.1093","volume":"190","author":[{"given":"Kyunghee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]},{"name":"Aging-Associated Vascular Disease Research Center, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]},{"name":"Aging-Associated Vascular Disease Research Center, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keuk-Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Taekyeung College , Gyeungsan 712-719,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoogeun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National Creative Research Initiatives Center, Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology , Daejeon 305-701,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-In","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Institute for Hard Tissue and Bio-Tooth Regeneration, School of Dentristry, Kyungpook National University , Daegu 700-412,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute of Medical Engineering, Yonsei University , Wonju 220-710,","place":["Korea"]},{"name":"Yonsei-Fraunhofer Medical Device Laboratory, Yonsei University , Wonju 220-710,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghyun","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute of Medical Engineering, Yonsei University , Wonju 220-710,","place":["Korea"]},{"name":"Yonsei-Fraunhofer Medical Device Laboratory, Yonsei University , Wonju 220-710,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Kook","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chonnam National University Medical School , Gwangju 501-746,","place":["Korea"]},{"name":"Medical Research Center for Gene Regulation, Chonnam National University Medical School , Gwangju 501-746,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Hyeon","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chonnam National University Medical School , Gwangju 501-746,","place":["Korea"]},{"name":"Medical Research Center for Gene Regulation, Chonnam National University Medical School , Gwangju 501-746,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daewon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]},{"name":"Aging-Associated Vascular Disease Research Center, Yeungnam University College of Medicine , Daegu 705-717,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,15]]},"reference":[{"key":"2025032406340314900_r1","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.2215\/CJN.05910809","article-title":"Calcium metabolism in health and disease","volume":"5","author":"Peacock","year":"2010","journal-title":"Clin. 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