These results suggest that DKK1 may play a key role in the development of MM-associated OBL by directly interrupting Wnt-regulated differentiation of osteoblasts and indirectly increasing osteoclastogenesis via a DKK1-mediated increase in RANKL-to-OPG ratios.
We conclude that DKK1 is a key player in MM bone disease and that blocking DKK1 activity in myelomatous bones reduces osteolytic bone resorption, increases bone formation, and helps control MM growth.
We conclude that specific strategies to modulate persistent activation of the JNK pathway may be beneficial in preventing disease progression and treating myeloma-associated bone disease by inhibiting DKK1 expression.
In 60 multiple myeloma patients checked, we found that among the Wnt inhibitors, Dickkopf-1 and secreted frizzled-related protein-3 were produced by multiple myeloma cells.
Additionally, we show that the >5-kDa fraction of MSC-conditioned medium promotes the proliferation of Dickkopf-1-secreting MM cells and that an interleukin-6 (IL-6)-neutralizing antibody blocks this effect.