Osteogenic differentiation of mesenchymal stem cells in multiple myeloma: Identification of potential therapeutic targets

 Several mechanisms are potentially involved in multiple myeloma (MM)–induced inhibition of osteoblast formation and differentiation. MM cells inhibit osteoblastogenesis by blocking Runx2 activity in mesenchymal and osteoprogenitor cells through direct cell-to-cell contact with the involvement of very late antigen 4 (VLA-4)/vascular cell adhesion molecule 1 (VCAM-1). Soluble factors as interleukin (IL)-7 may contribute to the suppression of Runx2 activity by MM cells. Direct production of the Wnt inhibitor Dickkopf-1 (DKK-1), secreted frizzled related protein (sFRP)-3, and rarely sFRP-2 by MM cells as well as the overproduction of hepatocyte growth factor could inhibit osteoblast formation. Finally, IL-3 overproduction in the MM microenvironment is involved in the inhibition of osteoblast formation and differentiation.