Fluid Shear Stress Increases Osteocyte and Inhibits Osteoclasts via Downregulating Receptor-Activator of Nuclear Factor κB (RANK)/Osteoprotegerin Expression in Myeloma Microenvironment

BACKGROUND: The aim of this study was to determine the effects of myeloma cells exposed to fluid shear stress on osteocytes and osteoclasts, and clarify the potential underlying mechanisms. MATERIAL/METHODS: A flow and a non-flow model were established using a flow fluid chamber. The myeloma cell line U266 and murine osteocytic MLO-Y4 cells were cultured in vitro. The osteocytes and osteoclasts were examined under a microscope. Osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) activity. RANKL and osteoprotegerin (OPG) gene expression were detected using reverse transcription-quantitative polymerase chain reaction. RESULTS: Compared with the controls, Y4 cells cultured with U266 culture supernatant showed altered morphology, fewer osteocytes, increased RANKL gene expression, a higher RANKL/OPG gene ratio, and a greater number of TRAP-positive osteoclasts (P<0.05 for all). Compared to the no-flow model, the flow model showed a higher number of Y4 cells, increased OPG gene expression, decreased RANKL gene expression, a lower RANKL/OPG gene ratio, and fewer TRAP-positive osteoclasts (P<0.05 for all). CONCLUSIONS: Our study revealed that fluid shear stress ameliorated the inhibitory effects of myeloma cells on osteocyte growth and inhibited osteoclast proliferation by means of decreasing RANKL/OPG gene expression. This may have clinical implications in patients with multiple myeloma in that mechanical loading with low-intensity vibration or mild exercise may prevent the progression of myeloma bone disease.