Vaspin prevents leptin-induced inflammation and catabolism by inhibiting the activation of nuclear factor-κB in rat chondrocytes
Vaspin prevents leptin-induced inflammation and catabolism by inhibiting the activation of nuclear factor-κB in rat chondrocytes
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DOI：
10.3892/mmr.2017.6911
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发表时间：
2017-09-01
影响因子：
3.4
通讯作者：
Wu, Li-Dong
中科院分区：
文献类型：
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作者：
Bao, Jia-Peng;Xu, Lang-Hai;Wu, Li-Dong
本研究旨在探讨不同浓度的内脏脂肪组织来源的丝氨酸蛋白酶抑制剂（vaspin）对瘦素诱导的大鼠软骨细胞炎症和代谢反应的作用及其可能的机制。分离大鼠关节软骨细胞，用不同浓度的vaspin处理，然后用瘦素刺激。通过逆转录-定量聚合酶链反应、ELISA和Western印迹分析基因表达、一氧化氮和肿瘤坏死因子-α的分泌以及核因子（NF）-κ B通路的激活。结果表明，vaspin以剂量依赖性方式抑制瘦素诱导的瘦素受体（OB-Rb）、具有血小板反应蛋白基序的去整合素和金属蛋白酶（ADAMTS）-4、ADAMTS-5、基质金属蛋白酶（MMP）-2和MMP-9的基因表达水平上调，以及NO和TNF-α的分泌。瘦素还促进软骨细胞中NF-κ B抑制剂（I kappa B）、I kappa B激酶（IKK）α、IKK β和NF-κ B的磷酸化，而增加浓度的vaspin也抑制这些磷酸化。总而言之，结果表明，vaspin通过抑制大鼠软骨细胞中NF-κ B的活化来预防瘦素诱导的炎症和分解代谢。
The present study aimed to investigate the function and possible underlying mechanism of various concentrations of visceral adipose tissue-derived serine protease inhibitor (vaspin) on leptin-induced inflammatory and metabolic responses in rat chondrocytes. Rat articular chondrocytes were isolated and treated with different concentrations of vaspin, which was followed by stimulation with leptin. The expression of genes, secretion of nitric oxide and tumor necrosis factor-alpha, and activation of the nuclear factor (NF)-kappa B pathway were analyzed by reverse transcription-quantitative polymerase chain reaction, ELISA and western blotting. The results demonstrated that vaspin inhibited the leptin-induced upregulated gene expression levels of leptin receptor (OB-Rb), a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-2 and MMP-9, and the secretion of NO and TNF-alpha, in a dose-dependent manner. The phosphorylation of inhibitor of NF-kappa B (I kappa B), I kappa B kinase (IKK)a, IKK ss and NF-kappa B were also promoted by leptin in the chondrocytes, which were also suppressed by increased concentration of vaspin. Taken together, results demonstrated that vaspin prevented leptin-induced inflammation and catabolism by inhibiting the activation of NF-kappa B in rat chondrocytes.