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内脏脂肪组织衍生的丝氨酸蛋白酶抑制剂可抑制白细胞介素-1β诱导的小鼠软骨细胞分解代谢和炎症反应。

Visceral adipose tissue-derived serine protease inhibitor inhibits interleukin-1β-induced catabolic and inflammatory responses in murine chondrocytes.

作者信息

Bao Jia-Peng, Jiang Li-Feng, Li Jing, Chen Wei-Ping, Hu Peng-Fei, Wu Li-Dong

机构信息

Department of Orthopedics Surgery, The Second Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

出版信息

Mol Med Rep. 2014 Oct;10(4):2191-7. doi: 10.3892/mmr.2014.2478. Epub 2014 Aug 11.

DOI:10.3892/mmr.2014.2478
PMID:25118941
Abstract

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a newly identified member of the adipocytokine family, whose precise role in chondrocyte metabolism remains to be elucidated. The aim of the present study was to investigate the effect of vaspin on chondrocytes. The cell viability and the cytotoxicity of vaspin in chondrocytes were examined. Furthermore, the gene expression of matrix metalloproteinases-2 and -9, a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 and cathepsin D was also examined, as well as the protein production of cyclooxygenase-2, prostaglandin E2 and inducible nitrous oxide synthase following treatment with different concentrations of vaspin in the absence or presence of interleukin-1-beta (IL-1β). In addition, the protein levels of the inhibitor of nuclear factor-κB (IκB-α) and the phosphorylation of nuclear factor kappa B (NF‑κB) were investigated. Vaspin was not able to stimulate the proliferation of chondrocytes and demonstrated no significant cytotoxic effect at concentrations of 10-500 ng/ml following coincubation for 24 and 48 h. However, vaspin inhibited IL-1β‑induced production of catabolic factors and inflammatory mediators in chondrocytes, and also suppressed the phosphorylation of NF‑κB and the degradation of IκB‑α. The data from the present study suggested that vaspin has a protective effect in chondrocyte metabolism and is an important factor in the pathophysiology of osteoarthritis.

摘要

内脏脂肪组织衍生的丝氨酸蛋白酶抑制剂(内脏脂肪素)是脂肪细胞因子家族新发现的成员,其在软骨细胞代谢中的精确作用尚待阐明。本研究旨在探讨内脏脂肪素对软骨细胞的影响。检测了内脏脂肪素在软骨细胞中的细胞活力和细胞毒性。此外,还检测了基质金属蛋白酶-2和-9、含血小板反应蛋白基序的解聚素和金属蛋白酶4和5以及组织蛋白酶D的基因表达,以及在存在或不存在白细胞介素-1β(IL-1β)的情况下用不同浓度的内脏脂肪素处理后环氧合酶-2、前列腺素E2和诱导型一氧化氮合酶的蛋白产生。此外,还研究了核因子-κB抑制剂(IκB-α)的蛋白水平和核因子κB(NF-κB)的磷酸化情况。内脏脂肪素不能刺激软骨细胞增殖,在10-500 ng/ml浓度下共孵育24和48小时后未显示出明显的细胞毒性作用。然而,内脏脂肪素抑制IL-1β诱导的软骨细胞中分解代谢因子和炎症介质的产生,还抑制NF-κB的磷酸化和IκB-α的降解。本研究数据表明,内脏脂肪素在软骨细胞代谢中具有保护作用,是骨关节炎病理生理学中的一个重要因素。

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