MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway.
MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway.
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DOI：
10.1177/0963689720939131
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发表时间：
2020-01
影响因子：
3.3
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Chen S;Li B
在骨关节炎（OA）中，细胞外基质（ECM）的合成和分解不平衡。wnt1诱导的信号通路蛋白1 （WISP1）高表达可促进基质金属蛋白酶的合成，诱导软骨降解，从而加重OA。本研究旨在探讨miR-128-3p在OA发生发展中的作用。本研究采用定量反转录PCR （RT-qPCR）和Western blotting检测骨关节炎组织和软骨细胞中WISP1和miR-128-3p的表达。然后我们通过TargetScan预测WISP1可能是miR-128-3p的潜在靶基因，并通过荧光素酶报告基因实验进行验证。通过细胞增殖试验、细胞凋亡试验和caspase-3活性试验评估miR-128-3p或WISP1对软骨细胞的影响。为了进一步揭示miR-128-3p在骨关节炎发生发展中的分子机制，我们采用ELISA法检测骨关节炎软骨细胞模型中软骨基质的降解和促炎细胞因子的产生。在体外模拟骨关节炎微环境的研究中，我们用白细胞介素(IL)-1β刺激软骨细胞，然后我们发现miR-128-3p的表达下调。WISP1过表达抑制软骨细胞增殖，诱导细胞凋亡、软骨细胞基质降解、促炎细胞因子产生，激活活化B细胞的磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B (Akt)/核因子κB轻链增强子（NF-κB）通路。然后，我们发现miR-128-3p是WISP1的负调控因子，直接靶向其3 ' -未翻译区（UTR）。此外，PI3K变构激活剂740 Y-P消除了miR-128-3p对细胞凋亡、软骨细胞基质降解和炎症的抑制作用。我们的研究结果表明，miR-128-3p通过PI3K/Akt/NF-κB通路靶向WISP1，调控软骨细胞增殖、凋亡、软骨细胞基质降解和促炎细胞因子的产生，在OA中起抑制作用。
In osteoarthritis (OA), the synthesis and decomposition of the extracellular matrix (ECM) are imbalanced. High expression levels of Wnt1-inducible signaling pathway protein 1 (WISP1) promote the synthesis of matrix metalloproteinases and induce the degradation of cartilage, which aggravates the OA. The aim of this study was to explore the role of miR-128-3p in the development of OA. In the present study, the expression of WISP1 and miR-128-3p in osteoarthritic tissues and chondrocytes was detected using quantitative reverse transcription PCR (RT-qPCR) and Western blotting. Then we predicted that WISP1 might be a potential target gene of miR-128-3p by TargetScan and verified using luciferase reporter gene assay. The effect of miR-128-3p or WISP1 on chondrocytes was evaluated by cell proliferation assay, apoptosis, and caspase-3 activity assay. To further reveal the molecular mechanisms of miR-128-3p in osteoarthritic development, the degradation of chondrocyte matrix and production of proinflammatory cytokines in osteoarthritic chondrocyte model were detected by ELISA. To mimic the osteoarthritic microenvironment in vitro studies, chondrocytes were stimulated with interleukin (IL)-1β, and then we found that the expression of miR-128-3p was downregulated. Overexpression of WISP1 inhibited the proliferation of chondrocytes, which induced apoptosis, degradation of chondrocyte matrix, production of proinflammatory cytokines, and activated the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Then, we identified that miR-128-3p was a negative regulator of WISP1 by directly targeting its 3′-untranslated region (UTR). Moreover, the PI3K allosteric activator 740 Y-P abolished the inhibition of miR-128-3p in apoptosis, degradation of chondrocyte matrix, and inflammation. Our results showed that miR-128-3p targets WISP1 to regulate chondrocyte proliferation, apoptosis, degradation of chondrocyte matrix, and production of proinflammatory cytokines via the PI3K/Akt/NF-κB pathway, which plays a suppressed role in OA.
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影响因子：
5.8
作者：
Maiese K;Chong ZZ;Shang YC;Wang S
通讯作者：
Wang S
影响因子：
3.7
作者：
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影响因子：
11.5
作者：
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