{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:34:12Z","timestamp":1791275652304,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2012,7,13]],"date-time":"2012-07-13T00:00:00Z","timestamp":1342137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteoporosis is characterized by enhanced differentiation of bone-resorbing osteoclasts, resulting in a rapid loss of functional trabecular bone. Bone-forming osteoblasts and osteoblast-derived osteocytes perform a key role in the regulation of osteoclast development by providing both the pro-osteoclastogenic cytokine receptor activator of NF-\u03baB ligand (RANKL) and its natural decoy receptor osteoprotegerin (OPG). By regulating the RANKL\/OPG ratio, osteoblasts hence determine the rate of both osteoclast differentiation and bone turnover. Here, we describe a novel role for liver X receptors (LXRs) during the crosstalk of bone-forming osteoblasts and bone-resorbing osteoclasts. By using a system of osteoblast\/osteoclast cocultures, we identify LXRs as regulator of RANKL expression and the RANKL\/OPG ratio in osteoblasts. Activation of LXRs drastically reduced the RANKL\/OPG ratio and interfered with osteoblast-mediated osteoclast differentiation in vitro. During an ovariectomy (OVX)-induced model of postmenopausal osteoporosis, the application of an LXR agonist shifted the RANKL\/OPG ratio in vivo, ameliorated the enhanced osteoclast differentiation, and provided complete protection from OVX-induced bone loss. These results reveal an unexpected involvement of LXRs in the regulation of bone turnover and highlight a potential role for LXRs as novel targets in the treatment of osteoporosis and related diseases. \u00a9 2012 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.1702","type":"journal-article","created":{"date-parts":[[2012,7,14]],"date-time":"2012-07-14T03:06:10Z","timestamp":1342235170000},"page":"2442-2451","source":"Crossref","is-referenced-by-count":40,"title":["Liver X receptors orchestrate osteoblast\/osteoclast crosstalk and counteract pathologic bone loss"],"prefix":"10.1093","volume":"27","author":[{"given":"Arnd","family":"Kleyer","sequence":"first","affiliation":[{"name":"Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Scholtysek","sequence":"additional","affiliation":[{"name":"Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Bottesch","sequence":"additional","affiliation":[{"name":"Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Hillienhof","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beyer","sequence":"additional","affiliation":[{"name":"Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg HW","family":"Distler","sequence":"additional","affiliation":[{"name":"Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany"},{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan 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