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. 2014 May 9;30(11):1085–1102. doi: 10.1002/cnm.2645

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© 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Proposed cellular interactions in multiple myeloma (MM) development. (1) Bone marrow stromal cell (BMSC)-MM cells adhesion enhances the production of interleukin-6 (IL-6) by BMSCs ²⁴; (2) transforming growth factor-beta (TGF-β) stimulates the production of IL-6 ²⁵^,²⁶; (3) IL-6 stimulates the proliferation of MM cells ²⁵^–²⁷; (4) immature osteoblasts support the growth and survival of MM cells, whereas mature osteoblasts enhance the apoptosis of MM cells; (5) the blockade of differentiation into mature osteoblasts contributes to the increase of the ratio of receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANKL/OPG) and thus promotes osteoclasts proliferation; (6) and TGF-β potentially inhibits later phases of osteoblast differentiation and maturation. For further information on the significance of the different colours and solid/hollow connecting lines, see the main text.