{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:57:28Z","timestamp":1785794248769,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hertha Nathorff Foundation of Ulm University","award":["LSSH1000.19"],"award-info":[{"award-number":["LSSH1000.19"]}]},{"name":"Hertha Nathorff Foundation of Ulm University","award":["251293561"],"award-info":[{"award-number":["251293561"]}]},{"name":"Hertha Nathorff Foundation of Ulm University","award":["C01 INST 40\/491-1"],"award-info":[{"award-number":["C01 INST 40\/491-1"]}]},{"name":"Collaborative Research Center 1149 \u201cDanger Response, Disturbance Factors and Regenerative Potential After Acute Trauma\u201d","award":["LSSH1000.19"],"award-info":[{"award-number":["LSSH1000.19"]}]},{"name":"Collaborative Research Center 1149 \u201cDanger Response, Disturbance Factors and Regenerative Potential After Acute Trauma\u201d","award":["251293561"],"award-info":[{"award-number":["251293561"]}]},{"name":"Collaborative Research Center 1149 \u201cDanger Response, Disturbance Factors and Regenerative Potential After Acute Trauma\u201d","award":["C01 INST 40\/491-1"],"award-info":[{"award-number":["C01 INST 40\/491-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NF\u03baB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss.<\/jats:p>","DOI":"10.3390\/ijms24119135","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T08:14:28Z","timestamp":1684829668000},"page":"9135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Role of Mast-Cell-Derived RANKL in Ovariectomy-Induced Bone Loss in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-8008","authenticated-orcid":false,"given":"Verena","family":"Fischer","sequence":"first","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin Maria","family":"B\u00fclow","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Thilo","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-1872","authenticated-orcid":false,"given":"Deniz","family":"Ragipoglu","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vikman","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3333-2613","authenticated-orcid":false,"given":"Melanie","family":"Haffner-Luntzer","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Katsoulis-Dimitriou","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-9620","authenticated-orcid":false,"given":"Anne","family":"Dudeck","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-1979","authenticated-orcid":false,"given":"Anita","family":"Ignatius","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11657-020-00871-9","article-title":"SCOPE 2021: A new scorecard for osteoporosis in Europe","volume":"16","author":"Kanis","year":"2021","journal-title":"Arch. 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