{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:25:04Z","timestamp":1791228304577,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione","award":["CUPB84I18000540002"],"award-info":[{"award-number":["CUPB84I18000540002"]}]},{"name":"Research Center of Excellence for Neurodegenerative Diseases and Brain Aging","award":["DM 1557 11.10.2022"],"award-info":[{"award-number":["DM 1557 11.10.2022"]}]},{"name":"National Recovery and Resilience Plan, Investment PE8\u2014Project Age-It","award":["CUP: B83C22004800006"],"award-info":[{"award-number":["CUP: B83C22004800006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bone disease associated with multiple myeloma (MM) is characterized by osteolytic lesions and pathological fractures, which remain a therapeutic priority despite new drugs improving MM patient survival. Antiresorptive molecules represent the main option for the treatment of MM-associated bone disease (MMBD), whereas osteoanabolic molecules are under investigation. Among these latter, we here focused on the myokine irisin, which is able to enhance bone mass in healthy mice, prevent bone loss in osteoporotic mouse models, and accelerate fracture healing in mice. Therefore, we investigated irisin effect on MMBD in a mouse model of MM induced by intratibial injection of myeloma cells followed by weekly administration of 100\u00a0\u03bcg\/kg of recombinant irisin for 5\u00a0wk. By micro-Ct analysis, we demonstrated that irisin improves MM-induced trabecular bone damage by partially preventing the reduction of femur Trabecular Bone Volume\/Total Volume (P\u2009=\u2009.0028), Trabecular Number (P\u2009=\u2009.0076), Trabecular Fractal Dimension (P\u2009=\u2009.0044), and increasing Trabecular Separation (P\u2009=\u2009.0003) in MM mice. In cortical bone, irisin downregulates the expression of Sclerostin, a bone formation inhibitor, and RankL, a pro-osteoclastogenic molecule, while in BM it upregulates Opg, an anti-osteoclastogenic cytokine. We found that in the BM tibia of irisin-treated MM mice, the percentage of MM cells displays a reduction trend, while in the femur it decreases significantly. This is in line with the in vitro reduction of myeloma cell viability after 48\u00a0h of irisin stimulation at both 200 and 500\u00a0ng\/mL and, after 72\u00a0h already at 100\u00a0ng\/mL rec-irisin. These results could be due to irisin ability to downregulate the expression of Notch 3, which is important for cell-to-cell communication in the tumor niche, and Cyclin D1, supporting an inhibitory effect of irisin on MM cell proliferation. Overall, our findings suggest that irisin could be a new promising strategy to counteract MMBD and tumor burden in one shot.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae066","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T11:25:11Z","timestamp":1716463511000},"source":"Crossref","is-referenced-by-count":7,"title":["Irisin prevents trabecular bone damage and tumor invasion in a mouse model of multiple myeloma"],"prefix":"10.1093","volume":"8","author":[{"given":"Roberta","family":"Zerlotin","sequence":"first","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Oranger","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pignataro","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Dicarlo","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Sanesi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia , 71122 Foggia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clelia","family":"Suriano","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Storlino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia , 71122 Foggia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mestice","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sante","family":"Di Gioia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia , 71122 Foggia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia , 71122 Foggia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Grano","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Colaianni","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Colucci","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari , 70124 Bari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"issue":"2","key":"2024060913315672200_ref1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/jcb.22403","article-title":"Pathogenesis of myeloma bone disease","volume":"109","author":"Roodman","year":"2010","journal-title":"J Cell Biochem"},{"issue":"5","key":"2024060913315672200_ref2","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/leu.2010.62","article-title":"Prognostic variables for survival and skeletal complications in patients with multiple myeloma osteolytic bone disease","volume":"24","author":"Terpos","year":"2010","journal-title":"Leukemia"},{"issue":"8","key":"2024060913315672200_ref3","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1002\/cncr.22991","article-title":"Pathologic fractures correlate with reduced survival in patients with malignant bone disease","volume":"110","author":"Saad","year":"2007","journal-title":"Cancer"},{"issue":"2","key":"2024060913315672200_ref4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.6004\/jadpro.2023.14.2.5","article-title":"Physical activity in multiple myeloma: a review of the current literature","volume":"14","author":"Hillengass","year":"2023","journal-title":"J Adv Pract Oncol"},{"issue":"3","key":"2024060913315672200_ref5","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S1470-2045(18)30072-X","article-title":"Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study","volume":"19","author":"Raje","year":"2018","journal-title":"Lancet Oncol"},{"issue":"4","key":"2024060913315672200_ref6","first-page":"264","article-title":"Pathophysiology and therapeutic advances in myeloma bone 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