American Society of Hematology

Fig. 1.

$Fig. 1. Interactions of the RANKL-OPG system with myeloma cells, bone marrow stromal cells, and osteoclasts in the pathogenesis of myeloma bone disease. / Myeloma cells express RANKL (1) and cause bone marrow–residing stromal cells to overexpress RANKL (2). In addition, myeloma cells inhibit OPG production by stromal cells (3). Syndecan-1 is expressed on the surface of myeloma cells and binds the heparin-binding domain of OPG (4), thus facilitating internalisation and lysosomal degradation of OPG (5). The physiologic balance between RANKL and OPG is tilted by these combined effects (6), and the ensuing enhanced RANKL-to-OPG ratio promotes osteoclast formation and activation, which is responsible for osteolysis, hypercalcemia, fractures, and pain. OPG indicates osteoprotegerin; RANKL, receptor activator of NF-κB ligand; RANK, receptor activator of NF-κB.$

Interactions of the RANKL-OPG system with myeloma cells, bone marrow stromal cells, and osteoclasts in the pathogenesis of myeloma bone disease.

Myeloma cells express RANKL (1) and cause bone marrow–residing stromal cells to overexpress RANKL (2). In addition, myeloma cells inhibit OPG production by stromal cells (3). Syndecan-1 is expressed on the surface of myeloma cells and binds the heparin-binding domain of OPG (4), thus facilitating internalisation and lysosomal degradation of OPG (5). The physiologic balance between RANKL and OPG is tilted by these combined effects (6), and the ensuing enhanced RANKL-to-OPG ratio promotes osteoclast formation and activation, which is responsible for osteolysis, hypercalcemia, fractures, and pain. OPG indicates osteoprotegerin; RANKL, receptor activator of NF-κB ligand; RANK, receptor activator of NF-κB.

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