Fig. 2

Bone homeostasis and multiple myeloma-induced osteolytic bone disease. (In black) In the BM, Wnt ligands are expressed by MSCs, endothelial cells, BM stromal cells, immune cells including macrophages and dendritic cells, osteoblasts and osteoclast. Wnts promote differentiation of MSCs towards the osteoblastic lineage, stimulate osteoblast proliferation, and promote osteoblast survival. Osteoblasts regulate osteoclast activity by secreting the antagonistic molecules RANKL and OPG, and Wnt5. Osteoclasts also regulate osteoblast function by secreting Wnt10b. Through this system, osteoblast and osteoclast activity is coupled and bone homeostasis is maintained. Osteoblasts also inhibit MM cell growth by expressing decorin. (In red) MM cells promote osteoclast function by secreting RANKL. Osteoclasts stimulate MM cells by secreting IL-6 and Annexin II. Enhanced bone resorption also leads to increased IGF-1 and TGF-β levels. MM cells also inhibit osteoblasts by secreting Wnt inhibitors sFRP2 and Dkk1. This disrupts the osteoblast-osteoclast balance and bone homeostasis and leads to osteolytic bone disease