Hydrostatic pressure influences HIF-2 alpha expression in chondrocytes.
Hydrostatic pressure influences HIF-2 alpha expression in chondrocytes.
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DOI：
10.3390/ijms16011043
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发表时间：
2015-01-05
影响因子：
5.6
通讯作者：
Kubo T
中科院分区：
文献类型：
--
作者：
Inoue H;Arai Y;Kishida T;Terauchi R;Honjo K;Nakagawa S;Tsuchida S;Matsuki T;Ueshima K;Fujiwara H;Mazda O;Kubo T
低氧诱导因子-2α被认为在骨关节炎的进展中起重要作用。最近有报道称，压力幅值影响小鼠内皮细胞缺氧诱导因子-2α的表达。我们检测了静水压力是否与关节软骨细胞中缺氧诱导因子-2α的表达有关。软骨细胞用0、5、10或50 Mpa的炎症或静水压力进行培养和刺激。刺激后检测热休克蛋白70、低氧诱导因子-2α、核因子-κB、基质金属蛋白酶-13、基质金属蛋白酶-3和血管内皮生长因子基因的表达。炎症应激可使ALL基因表达水平升高。当软骨细胞暴露于5 Mpa的静水压力时，HIF-2α、MMP13和MMP3基因的表达显著增加，而HSP70和NF-κB的表达与对照组无显著差异。相反，HIF-2α基因的表达在50 Mpa的静水压力下并没有增加，但HSP70和NF-κB的表达显著高于对照组。我们认为，5 Mpa的静水压力可以调节HIF-2α的表达，而不依赖于NF-κB，因为在5 Mpa的静水压力下，HIF-2α的表达水平显著增加，而不上调Nf-κB的表达。静水压力可能影响软骨退变，通过HIF-2α诱导基质金属蛋白酶-13和基质金属蛋白酶-3的表达。
Hypoxia-inducible factor (HIF)-2α is considered to play a major role in the progression of osteoarthritis. Recently, it was reported that pressure amplitude influences HIF-2α expression in murine endothelial cells. We examined whether hydrostatic pressure is involved in expression of HIF-2α in articular chondrocytes. Chondrocytes were cultured and stimulated by inflammation or hydrostatic pressure of 0, 5, 10, or 50 MPa. After stimulation, heat shock protein (HSP) 70, HIF-2α, nuclear factor kappa B (NF-κB), matrix metalloproteinase (MMP)-13, MMP-3, and vascular endothelial growth factor (VEGF) gene expression were evaluated. The levels of all gene expression were increased by inflammatory stress. When chondrocytes were exposed to a hydrostatic pressure of 5 MPa, HIF-2α, MMP-13, and MMP-3 gene expression increased significantly although those of HSP70 and NF-κB were not significantly different from the control group. In contrast, HIF-2α gene expression did not increase under a hydrostatic pressure of 50 MPa although HSP70 and NF-κB expression increased significantly compared to control. We considered that hydrostatic pressure of 5 MPa could regulate HIF-2α independent of NF-κB, because the level of HIF-2α gene expression increased significantly without upregulation of NF-κB expression at 5 MPa. Hydrostatic pressure may influence cartilage degeneration, inducing MMP-13 and MMP-3 expression through HIF-2α.
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