Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling
Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling
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DOI：
10.1016/j.bone.2006.05.017
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发表时间：
2006-11-01
期刊：
影响因子：
4.1
通讯作者：
Jacobs, Christopher R.
中科院分区：
文献类型：
--
作者：
Kim, Chi Hyun;You, Lidan;Jacobs, Christopher R.
身体活动会造成骨骼变形，导致局部压力梯度，从而驱动组织间液流动。由于所施加载荷的循环性质，该流动本质上是振荡的。振荡流体流（OFF）可能通过对成骨细胞和破骨细胞的作用导致积极的骨重建，但其对破骨细胞生成的影响知之甚少。在这项研究中，OFF对NF-κ B B配体受体激活因子（RANKL）和骨保护素（OPG）表达的影响，这两种因子是破骨细胞分化的重要调节因子。另外。定量测定其对破骨细胞的影响。将ST-2鼠骨髓基质细胞接种在载玻片上，并用1.25-二羟维生素D-3培养以表达RANKL。将细胞暴露于各种持续时间的OFF，导致IPa的峰值剪切应力。进行时间过程和剂量反应研究，并使用实时RT-PCR定量RANKL、OPG mRNA水平。暴露于OFF的ST-2细胞也与RAW 264.7单核细胞共培养，并对破骨细胞数量进行定量。RANKL/OPG的下降在血流结束后立即达到最大，随着负荷持续时间的增加，OPG显著增加，RANKL下降，最长可达2 h。与对照（未加载）ST-2细胞与RAW 264.7细胞共培养相比，OFF导致ST-2细胞与RAW 264.7细胞共培养的破骨细胞形成减少。这些结果表明，OFF确实是骨重建的有效调节剂，并且通过抑制破骨细胞的形成，可能发生由负荷诱导的流体流动介导的向正骨重建的转变。(C)2006年爱思唯尔公司All rights reserved.
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-kappa B ligand (RANKL) and osteoprotegerin (OPG), two important regulators of osteoclast differentiation, were investigated. In addition. its effect on osteoclast fort-nation 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 I 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. (C) 2006 Elsevier Inc. All rights reserved.