{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:48:36Z","timestamp":1784731716727,"version":"3.55.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T00:00:00Z","timestamp":1566518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":69,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007903","name":"Bloodwise","doi-asserted-by":"publisher","award":["12053"],"award-info":[{"award-number":["12053"]}],"id":[{"id":"10.13039\/501100007903","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004876","name":"Sheffield Hospitals Charity","doi-asserted-by":"publisher","award":["153878"],"award-info":[{"award-number":["153878"]}],"id":[{"id":"10.13039\/501100004876","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Multiple myeloma is a plasma cell malignancy that causes debilitating bone disease and fractures, in which TGF\u03b2 plays a central role. Current treatments do not repair existing damage and fractures remain a common occurrence. We developed a novel low tumor phase murine model mimicking the plateau phase in patients as we hypothesized this would be an ideal time to treat with a bone anabolic. Using in vivo \u03bcCT we show substantial and rapid bone lesion repair (and prevention) driven by SD-208 (TGF\u03b2 receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266-GFP-luc myeloma. We discovered that lesion repair occurred via an intramembranous fracture repair-like mechanism and that SD-208 enhanced collagen matrix maturation to significantly improve fracture resistance. Lesion healing was associated with VEGFA expression in woven bone, reduced osteocyte-derived PTHrP, increased osteoblasts, decreased osteoclasts, and lower serum tartrate-resistant acid phosphatase 5b (TRACP-5b). SD-208 also completely prevented bone lesion development in mice with aggressive JJN3 tumors, and was more effective than an anti-TGF\u03b2 neutralizing antibody (1D11). We also discovered that SD-208 promoted osteoblastic differentiation (and overcame the TGF\u03b2-induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture-resistance with SD-208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.3859","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T16:48:55Z","timestamp":1566578935000},"page":"2311-2326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["TGF\u03b2 Inhibition Stimulates Collagen Maturation to Enhance Bone Repair and Fracture Resistance in a Murine Myeloma Model"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0175-1485","authenticated-orcid":false,"given":"Alanna C","family":"Green","sequence":"first","affiliation":[{"name":"Mellanby Centre for Bone Research University of Sheffield Medical School, University of Sheffield Sheffield 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Engineering University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-923X","authenticated-orcid":false,"given":"Michelle A","family":"Lawson","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone Research University of Sheffield Medical School, University of Sheffield Sheffield UK"},{"name":"Sheffield Myeloma Research Team, Department of Oncology and Metabolism Medical School, University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Chantry","sequence":"additional","affiliation":[{"name":"Department of Haematology Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital Sheffield UK"},{"name":"Mellanby Centre for Bone Research University of Sheffield Medical School, University of Sheffield Sheffield UK"},{"name":"Sheffield Myeloma Research Team, Department of Oncology and Metabolism Medical School, 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