Increased Osteoblastic Activity Suppressed Proliferation of Multiple Myeloma Plasma Cells

Study Design. In vitro experimental study. Objective. To investigate the impact of increased osteoblastic activity on the proliferation and survival of multiple myeloma (MM) plasma cells in vitro Summary of Background Data. MM is one of representative hematologic malignancies that cause skeletal-related events (SREs) and dysregulation of bone remodeling is known as a key pathomechanism of disease progression and skeletal-related events. However, decreased proliferation of MM at fracture sites is frequently noted in clinical situations regardless of systemic disease activity. Methods. Co-culture under various conditions was used to investigate effects of increased osteoblastic activity on survival and proliferation of MM plasma cells. MM plasma cells were cultured in culture media (control) and co-cultured with human mesenchymal stem cells (hMSCs, group I), osteoblasts (OBs) induced from hMSCs (group II) or bone morphogenic protein-2 (BMP-2, group III). Proliferation measured as extracellular signal-regulated kinase (ERK) and immunoglobulin G (Ig G) expression and apoptosis measured as fluorescence-activated cell sorting (FACS) with annexin V method, caspase-3, and stat-3 expression were assessed for cultured MM plasma cells, along with expression of sclerostin. Results. After 72hours of co-culture, group II and III showed decreased ERK expression compared with controls. Lower Ig G expression was also noted for groups II and III compared with controls. Group I did not show significantly decreased Ig G and ERK expression compared with controls. Expressions of caspase-3 in groups II and III were higher than controls. Co-culture with hMSCs showed decreased caspase-3 expression compared with control. FACS with annexin V showed higher apoptosis in groups II and III. Sclerostin expression was also decreased in osteoblastic conditions compared with the control and hMSCs co-culture condition. Conclusion. Collectively, our data suggest that increased osteoblastic conditions may provide not only prevention of SREs but also anti-tumor effects on MM cells in the bone marrow environment.