[The role of RANK/RANKL and OPG in multiple myeloma]

Multiple myeloma (MM) almost exclusively develops in the bone marrow and generates devastating bone destruction by osteoclasts (OCs) recruited around myeloma cells. The severity of bone disease correlates with tumor burden. The interaction between RANK, expressed on the surface of OCs, and RANKL, a key molecule in the regulation of osteoclastogenesis expressed on bone marrow stromal cells, plays a role in the development and activation of OCs, whereas OPG, a decoy receptor for RANKL secreted from stromal cells, inhibits RANKL/RANK signaling. Myeloma cells stimulate osteoclastogenesis by triggering an increase in RANKL and decrease in OPG in bone marrow cells. They also express syndecan-1, a molecule which binds and stimulates OPG degradation in myeloma cells. MM cells can themselves express RANKL which can interact directly with RANK on OCs to promote osteoclast formation in a stromal cell-independent manner. Moreover, myeloma cells may additionally inhibit osteoblastogenesis directly or indirectly. The mechanisms involved in these coordinated processes are described and discussed.