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Bone. 2006 Nov;39(5):1043-1047. doi: 10.1016/j.bone.2006.05.017. Epub 2006 Jul 24.

Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling.

Author information

1
Orthopaedic Bioengineering Laboratory, Department of Biomedical Engineering, Yonsei University, Wonju, Kangwon Do, Korea; Bone and Joint Rehabilitation R&D Center, Department of Veterans Affairs, Palo Alto, CA, USA; Cell and Molecular Biomechanics Laboratory, Department of Mechanical Engineering, Stanford University, Stanford, CA, USA. Electronic address: chihyun@yonsei.ac.kr.
2
Bone and Joint Rehabilitation R&D Center, Department of Veterans Affairs, Palo Alto, CA, USA; Cell and Molecular Biomechanics Laboratory, Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
3
School of Veterinary Medicine, Department of Anatomy, Physiology and Cell Biology, University of California, Davis, CA, USA.

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.

PMID:
16860618
DOI:
10.1016/j.bone.2006.05.017
[Indexed for MEDLINE]

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