Mechanical stimulation of chondrocytes regulates HIF-1α under hypoxic conditions
Mechanical stimulation of chondrocytes regulates HIF-1α under hypoxic conditions
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DOI：
10.1016/j.tice.2021.101574
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发表时间：
2021-06-30
期刊：
影响因子：
2.6
通讯作者：
Takahashi, Kenji
中科院分区：
文献类型：
--
作者：
Shimomura, Seiji;Inoue, Hiroaki;Takahashi, Kenji
我们研究了缺氧诱导因子(HIF)-1 α在机械刺激下对关节软骨的影响及其相关机制。从Wistar大鼠的膝关节、髋关节和肩关节的关节软骨中分离出软骨细胞，在缺氧（5% O-2）条件下承受20%的拉伸应力24小时。在缺氧的机械刺激下，HIF-1 α和聚集蛋白的表达显著增强，而在常氧的机械刺激下，HIF-1 α和聚集蛋白的表达没有显著改变。缺氧条件下机械应力增强HIF-1 α的核易位。在常氧和缺氧条件下，机械刺激组与无机械刺激组相比，具有血栓反应蛋白基序的崩解素和金属蛋白酶（ADAM-TS） 5的表达显著降低。然而，HIF-1 α下调可减轻缺氧条件下机械刺激介导的聚集蛋白和ADAM-TS5表达的变化。我们还分析了跑步机运动对大鼠膝关节关节软骨中HIF-1 α产生的影响。适度跑步组HIF-1 α的产生增加，而过度跑步组则下降到与对照组相同的水平。这表明HIF-1 α在缺氧条件下调节关节软骨对机械刺激和一般机械刺激的aggrecan和ADAM-TS5表达，同时控制软骨稳态。
We investigated the effects of hypoxia-inducible factor (HIF)-1 alpha on articular cartilage under mechanical stimulation and the associated mechanisms. Chondrocytes, isolated from articular cartilage from the knee, hip, and shoulder joints of Wistar rats, were subjected to 20 % tensile stress under hypoxic (5% O-2) conditions for 24 h. HIF-1 alpha and aggrecan expression was significantly enhanced with mechanical stimulation under hypoxia but not significantly altered with mechanical stimulation under normoxia. The nuclear translocation of HIF-1 alpha was enhanced by mechanical stress under hypoxia. Under both normoxia and hypoxia, a disintegrin and metalloproteinase with thrombospondin motifs (ADAM-TS) 5 expression was significantly reduced with mechanical stimulation compared to that in the group without mechanical stimulation. However, HIF-1 alpha knockdown mitigated changes in aggrecan and ADAM-TS5 expression mediated by mechanical stimulation under hypoxia. The effects of treadmill running on HIF-1 alpha production in the articular cartilage of rat knee joints were also analyzed. HIF-1 alpha production increased in the moderate running group and decreased to the same levels as those in the control group in the excessive running group. This suggests that HIF-1 alpha regulates aggrecan and ADAM-TS5 expression in response to mechanical stimulation under hypoxia and general mechanical stimulation in articular cartilage under hypoxia, while controlling cartilage homeostasis.