Osteoblast impairment occurs within multiple myeloma cell infiltration into the 
bone marrow. Canonical Wnt signaling activation in osteoprogenitor cells is 
involved in osteoblast formation through the stabilization of dephosphorylated 
beta-catenin and its nuclear translocation. The effects of multiple myeloma 
cells on Wnt signaling in human mesenchymal/osteoprogenitor cells are unclear. 
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. However, although multiple myeloma cells or multiple myeloma bone 
marrow plasma affected expression of genes in the canonical Wnt signaling and 
inhibited beta-catenin stabilization in murine osteoprogenitor cells, they 
failed to block the canonical Wnt pathway in human mesenchymal or 
osteoprogenitor cells. Consistently, Wnt3a stimulation in human osteoprogenitor 
cells did not blunt the inhibitory effect of multiple myeloma cells on 
osteoblast formation. Consequently, despite the higher Wnt antagonist bone 
marrow levels in osteolytic multiple myeloma patients compared with 
nonosteolytic ones, beta-catenin immunostaining was not significantly different. 
Our results support the link between the production of Wnt antagonists by 
multiple myeloma cells and the presence of bone lesions in multiple myeloma 
patients but show that myeloma cells do not inhibit canonical Wnt signaling in 
human bone microenvironment.