Lee Mel S, Trindade Michael C D, Ikenoue Takashi, Schurman David J, Goodman Stuart B, Smith R Lane
Orthopaedic Research Laboratory and the Division of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, USA.
J Rheumatol. 2003 Feb;30(2):326-8.
To test the effects of intermittent hydrostatic pressure (IHP) on nitric oxide (NO) release induced by shear stress and matrix macromolecule gene expression in human osteoarthritic chondrocytes in vitro.
Chondrocytes isolated from cartilage samples from 9 patients with osteoarthritis were cultured and exposed to either shear stress or an NO donor. Nitrite concentration was measured using the Griess reaction. Matrix macromolecule mRNA signal levels were determined using reverse-transcriptase polymerase chain reaction and quantified by imaging analysis software.
Exposure to shear stress upregulated NO release in a dose and time-dependent manner. Application of IHP inhibited shear stress induced NO release but did not alter NO release from chondrocytes not exposed to shear stress. Shear stress induced NO or addition of an NO donor (sodium nitroprusside) was associated with decreased mRNA signal levels for the cartilage matrix proteins, aggrecan, and type II collagen. Intermittent hydrostatic pressure blocked the inhibitory effects of sodium nitroprusside but did not alter the inhibitory effects of shear stress on cartilage macromolecule gene expression.
Our data show that shear stress and IHP differentially alter chondrocyte metabolism and suggest that a balance of effects between different loading forces preserve cartilage extracellular matrix in vivo.
在体外测试间歇性流体静压（IHP）对人骨关节炎软骨细胞中剪切应力诱导的一氧化氮（NO）释放及基质大分子基因表达的影响。
从9例骨关节炎患者的软骨样本中分离软骨细胞，进行培养，并使其暴露于剪切应力或NO供体中。使用格里斯反应测量亚硝酸盐浓度。使用逆转录聚合酶链反应确定基质大分子mRNA信号水平，并通过成像分析软件进行定量。
暴露于剪切应力以剂量和时间依赖性方式上调NO释放。施加IHP可抑制剪切应力诱导的NO释放，但不改变未暴露于剪切应力的软骨细胞的NO释放。剪切应力诱导的NO或添加NO供体（硝普钠）与软骨基质蛋白、聚集蛋白聚糖和II型胶原的mRNA信号水平降低有关。间歇性流体静压可阻断硝普钠的抑制作用，但不改变剪切应力对软骨大分子基因表达的抑制作用。
我们的数据表明，剪切应力和IHP对软骨细胞代谢有不同影响，并表明不同加载力之间的效应平衡在体内维持软骨细胞外基质。
