title: The bone marrow stromal compartment in multiple myeloma patients retains capability for osteogenic differentiation in vitro: defining the stromal defect in myeloma.
abstract: Defects in bone repair contribute to multiple myeloma (MM) bone disease. It is unknown whether this reflects failure of osteogenic differentiation from mesenchymal stromal cells (MSC), inherent stromal defects or mature cell dysfunction. We quantified the number of fibroblast colony-forming units (CFU-f) and osteoblast colony-forming units (CFU-ob) in freshly isolated bone marrow (BM) from healthy individuals (N = 10) and MM patients (N = 54). CFU-f and CFU-ob were present in MM BM, at comparable frequency to normal subjects, irrespective of disease stage, and the presence of bone disease. Adherent cultures from MM BM are able to differentiate into osteoblasts, as indicated by the early upregulation of RUNX2, SP7, AXIN2 and DLX5, and the production of alkaline phosphatase and calcium. Coculture with MM cells failed to prevent osteogenic differentiation of adult human MSC. On the other hand, MM cells induced cell cycle progression in resting MSC in a cell contact dependent manner. This effect was confirmed using both primary CD138+ cells and MM 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, however dysregulation of cell cycle control may contribute to the loss of normal bone homeostasis that ultimately results in osteolytic bone loss.
authors: Department of Haematology, University College London, London, UK.
authors: Deepika
authors: D
authors: Kassen
authors: Sally
authors: S
authors: Moore
authors: Laura
authors: L
authors: Percy
authors: Gaelle
authors: G
authors: Herledan
authors: Danton
authors: D
authors: Bounds
authors: Manuel
authors: M
authors: Rodriguez-Justo
authors: Peter
authors: P
authors: Croucher
authors: Kwee
authors: K
authors: Yong
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002450:Cell Communication / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D018920:Coculture Techniques; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology* / Q000503:physiopathology; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
keywords: bone disease; mesenchymal stromal cells; multiple myeloma; osteoblasts