Department of Orthopedics, the Second Hospital of Ningbo, Ningbo, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2018 Apr;22(8):2454-2460. doi: 10.26355/eurrev_201804_14839.
As a common joint disease, osteoarthritis exhibits increasing trend in recent years. C-X-C motif chemokine receptor 3 (CXCR3) is a kind of chemokine with the characteristic of recruiting inflammatory cells. Its function in osteoarthritis has not been clarified. This study aims to explore the role of CXCR3 in cartilage injury by affecting unfolded protein response (UPR) pathway.
The sample was obtained from osteoarthritis patients to test CXCR3 expression by Real-time polymerase chain reaction (PCR). Chondrocyte apoptosis model was established in vitro induced by interleukin 1β (IL-1β) and sodium nitroprusside (SNP). CXCR3 level was downregulated by using siRNA. Cell apoptosis was determined by using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. UPR pathway related factors C/EBP homology protein (CHOP) and glucose regulated protein 78 (GRP78) protein expressions were tested by using Western blot.
CXCR3 protein level significantly increased in osteoarthritis patients (2.66 ± 0.25 vs. 1.00 ± 0.05, p<0.05). CXCR3 siRNA significantly reduced nitrate level in chondrocytes induced by IL-β (35.22 ± 1.76 vs. 17.82 ± 0.89, p<0.05) without affecting cell apoptosis (1.13 ± 0.05 vs. 0.859 ± 0.04, p>0.05). CXCR3 siRNA markedly downregulated nitrate level in chondrocytes (50.63 ± 2.53 vs. 30.63 ± 1.63, p<0.05) and alleviated cell apoptosis induced by SNP (1.98 ± 0.10 vs. 1.25 ± 0.06, p<0.05). UPR pathway C/EBP homology protein (CHOP) and glucose regulated protein 78 (GRP78) participated in the process of chondrocyte apoptosis.
Endoplasmic reticulum (ER) stress signaling pathway CHOP and GRP78 are involved in CXCR3 receptor attenuating chondrocyte apoptosis induced by SNP.
骨关节炎作为一种常见的关节疾病，近年来呈上升趋势。C-X-C 基序趋化因子受体 3（CXCR3）是一种趋化因子，具有募集炎症细胞的特征。其在骨关节炎中的作用尚不清楚。本研究旨在通过影响未折叠蛋白反应（UPR）途径探讨 CXCR3 在软骨损伤中的作用。
从骨关节炎患者中获取样本，通过实时聚合酶链反应（PCR）检测 CXCR3 表达。体外使用白细胞介素 1β（IL-1β）和亚硝基铁氰化钠（SNP）诱导软骨细胞凋亡模型。使用 siRNA 下调 CXCR3 水平。采用末端转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记（TUNEL）法检测细胞凋亡。Western blot 检测 UPR 途径相关因子 C/EBP 同源蛋白（CHOP）和葡萄糖调节蛋白 78（GRP78）的蛋白表达。
骨关节炎患者 CXCR3 蛋白水平显著升高（2.66±0.25 比 1.00±0.05，p<0.05）。CXCR3 siRNA 可显著降低 IL-β诱导的软骨细胞中硝酸盐水平（35.22±1.76 比 17.82±0.89，p<0.05），而不影响细胞凋亡（1.13±0.05 比 0.859±0.04，p>0.05）。CXCR3 siRNA 可显著降低软骨细胞中硝酸盐水平（50.63±2.53 比 30.63±1.63，p<0.05），减轻 SNP 诱导的细胞凋亡（1.98±0.10 比 1.25±0.06，p<0.05）。UPR 途径 C/EBP 同源蛋白（CHOP）和葡萄糖调节蛋白 78（GRP78）参与了软骨细胞凋亡过程。
内质网（ER）应激信号通路 CHOP 和 GRP78 参与了 CXCR3 受体减轻 SNP 诱导的软骨细胞凋亡。
