RRC ID 77495
Author Kim CH, You L, Yellowley CE, Jacobs CR.
Title Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling.
Journal Bone
Abstract Physical activity creates deformation in bone that leads to localized pressure gradients that drive interstitial fluid flow. Due to the cyclic nature of the applied load, this flow is oscillatory by nature. Oscillatory fluid flow (OFF) may lead to positive bone remodeling through effects on both osteoblasts and osteoclasts but its effect on osteoclastogenesis is poorly understood. In this study, the effects of OFF on expression of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), two important regulators of osteoclast differentiation, were investigated. In addition, its effect on osteoclast formation was quantified. ST-2 murine bone marrow stromal cells were plated on glass slides and cultured with 1,25-dihydroxyvitamin D(3) to express RANKL. Cells were exposed to various durations of OFF resulting in a peak shear stress of 1 Pa. Time course and dose-response studies were performed and real-time RT-PCR was used to quantify levels of RANKL, OPG mRNA. ST-2 cells exposed to OFF were also co-cultured with RAW 264.7 monocytes and osteoclast number quantified. Decrease in RANKL/OPG was maximal immediately after end of flow and there existed a significant increase in OPG and decrease in RANKL with increasing load duration of up to 2 h. OFF resulted in a decrease in osteoclast formation by ST-2 cells co-cultured with RAW 264.7 cells compared to co-culture of control (non-loaded) ST-2 cells with RAW 264.7 cells. These results suggest that indeed OFF is a potent regulator of bone remodeling, and that shift towards positive bone remodeling mediated by loading-induced fluid flow may occur via suppression of the formation of osteoclasts.
Volume 39(5)
Pages 1043-1047
Published 2006-11-1
DOI 10.1016/j.bone.2006.05.017
PII S8756-3282(06)00481-9
PMID 16860618
MeSH Animals Cell Line Cells, Cultured Coculture Techniques / methods Gene Expression Regulation / genetics Mice Monocytes / cytology Monocytes / metabolism Osteoclasts / cytology* Osteoclasts / metabolism Osteoprotegerin / genetics Osteoprotegerin / physiology* RANK Ligand / genetics RANK Ligand / physiology* RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics Signal Transduction / physiology* Stress, Mechanical Time Factors
IF 4.147
Human and Animal Cells ST2(RCB0224)