HIF-1α-Induced HSP70 Regulates Anabolic Responses in Articular Chondrocytes under Hypoxic Conditions
HIF-1α-Induced HSP70 Regulates Anabolic Responses in Articular Chondrocytes under Hypoxic Conditions
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DOI：
10.1002/jor.22623
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发表时间：
2014-08-01
影响因子：
2.8
通讯作者：
Kubo, Toshikazu
中科院分区：
文献类型：
--
作者：
Tsuchida, Shinji;Arai, Yuji;Kubo, Toshikazu
我们评估了热休克蛋白70（HSP 70）是否参与了缺氧条件下关节软骨细胞中缺氧诱导因子1 α（HIF-1 α）依赖的合成代谢途径。原代兔软骨细胞在常氧（20%氧条件）或缺氧（1%氧条件）下培养。或者，用诱导HIF-1 α的CoCl 2处理在常氧下培养的细胞以模拟缺氧，或在缺氧下用靶向HIF-1 α（si-HIF-1 α）和HSP 70（si-HSP 70）的siRNA转染。在低氧或模拟低氧条件下，HSP 70的表达通过增加HIF-1 α的表达而增强，但在si-HIF-1 α存在下不增强。缺氧诱导的ECM基因过表达被si-HIF-1 α或si-HSP 70显著抑制。细胞活力与缺氧呈正相关，但转染si-HIF-1 α或si-HSP 70可消除缺氧的软骨保护作用。虽然缺氧条件下硝普钠处理的细胞LDH释放和TUNEL阳性细胞比例降低，但si-HIF-1 α或si-HSP 70转染几乎完全阻断了这些作用。这些结果表明，HIF-1 α诱导的HSP 70过表达增加ECM基因的表达水平和细胞活力，并保护软骨细胞免于凋亡。HIF-1 α可能通过调节HSP 70的表达来调节低氧条件下软骨细胞的合成代谢作用。(C)2014骨科研究学会。出版社：Wiley Periodicals，Inc.
We assessed whether heat shock protein 70 (HSP70) is involved in hypoxia inducible factor 1 alpha (HIF-1 alpha)-dependent anabolic pathways in articular chondrocytes under hypoxic conditions. Primary rabbit chondrocytes were cultured under normoxia (20% oxygen condition) or hypoxia (1% oxygen condition). Alternatively, cells cultured under normoxia were treated with CoCl2, which induces HIF-1 alpha, to simulate hypoxia, or transfected with siRNAs targeting HIF-1 alpha (si-HIF-1 alpha) and HSP70 (si-HSP70) under hypoxia. HSP70 expression was enhanced by the increased expression of HIF-1 alpha under hypoxia or simulated hypoxia, but not in the presence of si-HIF-1 alpha. Hypoxia-induced overexpression of ECM genes was significantly suppressed by si-HIF-1 alpha or si-HSP70. Cell viability positively correlated with hypoxia, but transfection with si-HIF-1 alpha or si-HSP70 abrogated the chondroprotective effects of hypoxia. Although LDH release from sodium nitroprusside-treated cells and the proportion of TUNEL positive cells were decreased under hypoxia, transfection with si-HIF-1 alpha or si-HSP70 almost completely blocked these effects. These findings indicated that HIF-1 alpha-induced HSP70 overexpression increased the expression levels of ECM genes and cell viability, and protected chondrocytes from apoptosis. HIF-1 alpha may regulate the anabolic effects of chondrocytes under hypoxic conditions by regulating HSP70 expression. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.