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10 August 2019 : Laboratory Research  

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

Xiaotao Wang1ACDEFG*, Yuchan He1BDF, Shen Tian2BCD, Fangxiao Zhu3BF, Bo Huang1BE, Junyan Zhang1BF, Zhong Chen1BF, Hangfei Wang1BF

DOI: 10.12659/MSM.915986

Med Sci Monit 2019; 25:5961-5968

Abstract

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 AND 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.

Keywords: Multiple Myeloma, Osteoclasts, Osteocytes, RANK Ligand, Shear Strength, Biomechanical Phenomena, Gene Expression Regulation, hydrodynamics, Osteoprotegerin, Receptor Activator of Nuclear Factor-kappa B, Stress, Mechanical, tumor microenvironment

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750