{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:59:57Z","timestamp":1766066397873},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T00:00:00Z","timestamp":1406764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"UCL\/UCLH Biomedical Research Centre"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"Summary<\/jats:title>Defects in bone repair contribute to multiple myeloma (MM<\/jats:styled-content>) bone disease. It is unknown whether this reflects failure of osteogenic differentiation from mesenchymal stromal cells (MSC<\/jats:styled-content>), inherent stromal defects or mature cell dysfunction. We quantified the number of fibroblast colony\u2010forming units (CFU<\/jats:styled-content>\u2010f) and osteoblast colony\u2010forming units (CFU<\/jats:styled-content>\u2010ob) in freshly isolated bone marrow (BM<\/jats:styled-content>) from healthy individuals (N<\/jats:italic>\u00a0=\u00a010) and MM<\/jats:styled-content> patients (N<\/jats:italic>\u00a0=\u00a054). CFU<\/jats:styled-content>\u2010f and CFU<\/jats:styled-content>\u2010ob were present in MM BM<\/jats:styled-content>, at comparable frequency to normal subjects, irrespective of disease stage, and the presence of bone disease. Adherent cultures from MM BM<\/jats:styled-content> are able to differentiate into osteoblasts, as indicated by the early upregulation of RUNX<\/jats:styled-content>2<\/jats:italic>, SP<\/jats:styled-content>7, AXIN<\/jats:styled-content>2<\/jats:italic> and DLX<\/jats:styled-content>5<\/jats:italic>, and the production of alkaline phosphatase and calcium. Coculture with MM<\/jats:styled-content> cells failed to prevent osteogenic differentiation of adult human MSC<\/jats:styled-content>. On the other hand, MM<\/jats:styled-content> cells induced cell cycle progression in resting MSC<\/jats:styled-content> in a cell contact dependent manner. This effect was confirmed using both primary CD<\/jats:styled-content>138+ cells and MM<\/jats:styled-content> cell lines, and was not seen with B or T cell lines. Our data confirm the presence of osteoblast progenitors and the preservation of osteogenic function in MM<\/jats:styled-content>, however dysregulation of cell cycle control may contribute to the loss of normal bone homeostasis that ultimately results in osteolytic bone loss.<\/jats:p>","DOI":"10.1111\/bjh.13020","type":"journal-article","created":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T05:03:08Z","timestamp":1406782988000},"page":"194-206","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The bone marrow stromal compartment in multiple myeloma patients retains capability for osteogenic differentiation in vitro<\/i>: defining the stromal defect in myeloma"],"prefix":"10.1111","volume":"167","author":[{"given":"Deepika","family":"Kassen","sequence":"first","affiliation":[{"name":"Department of Haematology University College London London 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