Rheumatology Unit; Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, 53100 Siena, Italy.
Scleroderma Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy.
Int J Mol Sci. 2018 Dec 6;19(12):3909. doi: 10.3390/ijms19123909.
Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor ( in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased , , , and , and reduced and gene expression in OA chondrocytes. , , and were significantly modulated by treatment of OA chondrocytes with adipokines. Visfatin and resistin significantly increased NF-κB activation, while the co-treatment with BAY11-7082 did not change or levels beyond that caused by single treatment. Visfatin and resistin regulate the expression levels of some miRNA involved in OA pathogenesis and exert catabolic functions in chondrocytes via the pathway. These data confirm the complex relationship between adipokines and miRNA.
越来越多的证据表明脂肪因子和 microRNA(miRNA)在骨关节炎(OA)发病机制中起着重要作用。本研究的目的是探讨内脂素和抵抗素对人 OA 软骨细胞和 T/C-28a2 细胞系中某些 miRNA(34a、140、146a、155、181a、let-7e)、金属蛋白酶(MMPs)和 II 型胶原 α1 链(Col2a1)的影响。还评估了核因子(对脂肪因子的反应)的影响。用内脂素(5 或 10μg/mL)和抵抗素(50 或 100ng/mL)刺激软骨细胞,有或没有 NF-κB 抑制剂(BAY-11-7082,1μM)刺激 24 小时。通过 MTT 和细胞计数检测细胞活力和细胞凋亡,通过 qRT-PCR 检测 miRNA、MMP-1、MMP-13 和 Col2a1,通过免疫荧光检测 激活。内脂素和抵抗素显著降低 OA 软骨细胞活力,诱导细胞凋亡,增加 、 、 、 和 ,降低 和 基因表达。用脂肪因子处理 OA 软骨细胞可显著调节 、 、 和 。内脂素和抵抗素显著增加 NF-κB 激活,而用 BAY11-7082 共同处理不会使 或 水平超过单独处理引起的水平。内脂素和抵抗素调节参与 OA 发病机制的某些 miRNA 的表达水平,并通过 途径在软骨细胞中发挥分解代谢功能。这些数据证实了脂肪因子和 miRNA 之间的复杂关系。