{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:56:22Z","timestamp":1793890582784,"version":"4.8.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T00:00:00Z","timestamp":1720742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004876","name":"Sheffield Hospitals Charity","doi-asserted-by":"publisher","award":["222323"],"award-info":[{"award-number":["222323"]}],"id":[{"id":"10.13039\/501100004876","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004876","name":"Sheffield Hospitals Charity","doi-asserted-by":"publisher","award":["163969"],"award-info":[{"award-number":["163969"]}],"id":[{"id":"10.13039\/501100004876","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Weston Park Cancer Charity Clinical Research Fellowship"},{"name":"European Association of Cancer Research"},{"DOI":"10.13039\/501100000858","name":"University of Sheffield","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myeloma bone disease (MBD) affects ~90% of multiple myeloma patients, but current treatment options are suboptimal. Therefore, to successfully develop new therapies or optimize current ones, we must improve our fundamental knowledge of how myeloma affects bone microstructure and function. Here, we have investigated the osteocyte lacuno-canalicular network (LCN) in MBD, as bone porosity affects bone quality and resilience. We used the syngeneic 5TGM1-C57BL-Kalwrij and the xenograft U266-NSG models at end stage and compared them to healthy controls (na\u00efve). Micro-computed tomography (\u03bcCT) and histomorphometry indicated the 5TGM1 and U266 models developed mild and extensive MBD, respectively, with the U266 model producing large osteolytic lesions. High-resolution synchrotron micro-CT (SR-\u03bcCT) revealed significant osteocyte lacunae changes in U266 bones but not 5TGM1, with a reduction in lacunae number and sphericity, and an increase in lacunae volume compared with na\u00efve. Canalicular length, visualized using histological Ploton silver staining, appeared significantly shorter in 5TGM1 and U266 bones compared with na\u00efve. Canalicular area as a proportion of the bone was also decreased by 24.2% in the U266 model. We observed significant upregulation of genes implicated in peri-lacunar remodeling (PLR), but immunohistochemistry confirmed that the osteocyte-specific protein sclerostin, a known driver of PLR, was unchanged between MBD and na\u00efve bones. In summary, we have demonstrated evidence of PLR and altered organization of the osteocyte LCN in MBD mouse models. The next step would be to further understand the drivers and implications of PLR in MBD, and whether treatments to manipulate PLR and the LCN may improve patient outcomes.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae093","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T17:27:39Z","timestamp":1720805259000},"source":"Crossref","is-referenced-by-count":8,"title":["Evidence for peri-lacunar remodeling and altered osteocyte lacuno-canalicular network in mouse models of myeloma-induced bone disease"],"prefix":"10.1093","volume":"8","author":[{"given":"Holly","family":"Evans","sequence":"first","affiliation":[{"name":"University of Sheffield Division of Clinical Medicine and Mellanby Centre for Musculoskeletal Research, School of Medicine and Population Health, Faculty of Health, , Sheffield S10 2RX , United 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"Green","sequence":"additional","affiliation":[{"name":"University of Sheffield Division of Clinical Medicine and Mellanby Centre for Musculoskeletal Research, School of Medicine and Population Health, Faculty of Health, , Sheffield S10 2RX , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Chantry","sequence":"additional","affiliation":[{"name":"University of Sheffield Division of Clinical Medicine and Mellanby Centre for Musculoskeletal Research, School of Medicine and Population Health, Faculty of Health, , Sheffield S10 2RX , United Kingdom"},{"name":"Sheffield Teaching Hospitals, Royal Hallamshire Hospital NHS Foundation Trust Department of Haematology, , Sheffield S10 2JF , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Clarkin","sequence":"additional","affiliation":[{"name":"University of Southampton School of Biological Sciences, , Southampton SO17 1BJ , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Brown","sequence":"additional","affiliation":[{"name":"University of Sheffield Division of Clinical Medicine and Mellanby Centre for Musculoskeletal Research, School of Medicine and Population Health, Faculty of Health, , Sheffield S10 2RX , United Kingdom"},{"name":"Sheffield Teaching Hospitals, Royal Hallamshire Hospital NHS Foundation Trust Department of Haematology, , Sheffield S10 2JF , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-923X","authenticated-orcid":false,"given":"Michelle","family":"Lawson","sequence":"additional","affiliation":[{"name":"University of Sheffield Division of Clinical Medicine and Mellanby Centre for Musculoskeletal Research, School of Medicine and Population Health, Faculty of Health, , Sheffield S10 2RX , United 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