Possible chondroprotective effect of canakinumab: An in vitro study on human osteoarthritic chondrocytes
Possible chondroprotective effect of canakinumab: An in vitro study on human osteoarthritic chondrocytes
复制标题
DOI：
10.1016/j.cyto.2014.10.023
复制
发表时间：
2015-02-01
期刊：
影响因子：
3.8
通讯作者：
Fioravanti, Antonella
中科院分区：
文献类型：
--
作者：
Cheleschi, Sara;Cantarini, Luca;Fioravanti, Antonella
Canakinumab是一种人IgG κ单克隆抗体，可中和白细胞介素（IL）-1 β阻断与IL-1 β受体相互作用的活性。我们的研究旨在评估canakinumab对在存在或不存在肿瘤坏死因子（TNE）-α的情况下培养的人骨关节炎（OA）软骨细胞的体外作用。关节软骨取自骨关节炎（OA）患者的股骨头。将软骨细胞与两种浓度（1 μ g/ml和10 μ g/ml）的卡那单抗单独或与TNF-α（10 ng/ml）一起孵育48小时。透射电镜观察细胞活力、培养液中蛋白多糖（PG）和一氧化氮（NO）的释放、诱导型一氧化氮合酶（iNOS）和金属蛋白酶（MMP）1、3、13基因表达、细胞凋亡、坏死及形态学特征。卡那单抗单药不具有细胞毒性作用。在所用的两种浓度下，TNF-α显著降低细胞活力（p < 0.001），而卡那单抗恢复细胞活力。TNE-α测定PG的显著降低（p < 0.001）和NO的增加（p < 0.001）以及MMP-13，13基因表达。Canakinumab显著增加PG水平并降低（1 μ g/ml，p
Canakinumab is a human IgG kappa monoclonal antibody that neutralizes the activity of interleukin (IL)-1 beta blocking interaction with IL-1 beta receptors. Our study aimed to evaluate the in vitro effect of canakinumab on human osteoarthritic (OA) chondrocytes cultivated in the presence or absence of tumor necrosis factor (TNE)-alpha. Articular cartilage was obtained from the femoral heads of patients with osteoarthritis (OA). Chondrocytes were incubated with two concentrations (1 mu g/ml and 10 mu g/ml) of canakinumab alone or with TNF-alpha (10 ng/ml) for 48 h. We evaluated cell viability, release of proteoglycans (PG) and nitric oxide (NO) in culture medium, inducible nitric oxide synthase (iNOS) and metalloproteinanes (MMP)1,3,13 gene expression, apoptosis, necrosis and morphological feature by transmission electron microscopy (TEM). Canakinumab alone did not have cytotoxic effect. Cell viability was reduced significantly (p < 0.001) by TNF-alpha and restored by canakinumab at both concentrations used. TNE-alpha determined a significant decrease of PG (p < 0.001) and an increase of NO (p < 0.001) and MMP-13,13 gene expression. Canakinumab significantly increased the PG levels and decreased (1 mu g/ml, p