Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1.
Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1.
复制标题
microRNA-634 的过表达通过靶向 PIK3R1 抑制人骨关节炎软骨细胞的存活和基质合成。
DOI：
10.1038/srep23117
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发表时间：
2016-03-14
影响因子：
4.6
通讯作者：
Xia C
中科院分区：
文献类型：
--
作者：
Cui X;Wang S;Cai H;Lin Y;Zheng X;Zhang B;Xia C
骨关节炎（OA）是一种以关节软骨退化为特征的退行性疾病。最近的研究已经证明了一些microRNA在软骨损伤中的重要性。本研究的目的是鉴定和表征microRNA-634（miR-634）在正常和OA软骨细胞中的表达，并确定其在OA发病机制中的作用。体外培养人正常和OA软骨细胞。通过转染miR-634模拟物或抑制剂，研究miR-634对软骨细胞存活和基质合成的影响，并鉴定miR-634靶点。结果表明，与正常软骨细胞相比，miR-634在高度OA软骨细胞中的表达水平较低。miR-634过表达可抑制高度OA软骨细胞的存活和基质合成。此外，miR-634靶向编码I类PI 3 K调节亚基1（p85α）的PIK 3R 1基因，并在高级别OA软骨细胞中对Akt、mTOR和S6信号分子的磷酸化发挥其抑制作用。因此，数据表明，miR-634可以通过靶向PIK 3R 1基因来调节PI 3 K/Akt/S6和PI 3 K/Akt/mTOR/S6轴，从而抑制高级别OA软骨细胞的存活和基质合成，这对于验证miR-634作为OA治疗的潜在靶点具有重要意义。
Osteoarthritis (OA) is a degenerative disease characterized by deterioration of articular cartilage. Recent studies have demonstrated the importance of some microRNAs in cartilage damage. The aim of this study was to identify and characterize the expression of microRNA-634 (miR-634) in normal and OA chondrocytes, and to determine its role in OA pathogenesis. Human normal and OA chondrocytes obtained from patients were cultured in vitro. Transfection with miR-634 mimic or inhibitor was employed to investigate the effect of miR-634 on chondrocyte survival and matrix synthesis, and to identify miR-634 target. The results indicated that miR-634 was expressed at lower level in high grade OA chondrocyte compared with normal chondrocytes. Overexpression of miR-634 could inhibit cell survival and matrix synthesis in high grade OA chondrocytes. Furthermore, miR-634 targeted PIK3R1 gene that encodes the regulatory subunit 1 of class I PI3K (p85α) and exerted its inhibitory effect on the phosphorylation of Akt, mTOR, and S6 signal molecules in high grade OA chondrocytes. Therefore, the data suggested that miR-634 could suppress survival and matrix synthesis of high grade OA chondrocytes through targeting PIK3R1 gene to modulate the PI3K/Akt/S6 and PI3K/Akt/mTOR/S6 axes, with important implication for validating miR-634 as a potential target for OA therapy.