Wang Xipeng, Fan Jianbo, Ding Xiaomin, Sun Yuyu, Cui Zhiming, Liu Wei
Department of Orthopaedic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430010, People's Republic of China.
Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Drug Des Devel Ther. 2019 Oct 15;13:3559-3568. doi: 10.2147/DDDT.S216596. eCollection 2019.
Osteoarthritis (OA) is a prevalent degenerative joint disease, which was characterized by inflammation and cartilage degradation. Accumulating evidence has demonstrated that Tanshinone I has an anti-inflammatory effect in various diseases. However, the efficacy of Tanshinone I as an anti-inflammatory agent in OA remains unclear. This study aimed to explore the role of Tanshinone I on OA both in vitro and in vivo.
CHON-001 cells were treated with IL-1β (10 ng/mL) for 72 hrs to induce OA model in vitro. Meanwhile, CHON-001 cells were pre-treated with 20 μM Tanshinone I for 24 hrs and then stimulated with IL-1β (10 ng/mL) for 72 hrs. CCK-8, immunofluorescence and flow cytometry assays were used to detect the viability, proliferation and apoptosis in CHON-001 cells, respectively. Western blotting assay was used to detect the levels of collagen II, aggrecan, MMP-13, cleaved caspase 1, Gasdermin D, SOX11 and p-NF-κB in CHON-001 cells. In addition, the mouse model of OA was built by anterior cruciate ligament transection (ACLT) in the right knee. Meanwhile, the mice were administrated with 10 or 30 mg/kg Tanshinone I for 8 weeks. Safranin-O/Fast Green staining was used to assess cartilage destruction in a mouse model of OA.
In this study, IL-1β significantly induced apoptosis, extracellular matrix degradation and inflammatory response in CHON-001 cells. Tanshinone I significantly inhibited IL-1β-induced apoptosis in CHON-001 cells. In addition, the IL-1β-induced collagen II, aggrecan degradation, SOX11 downregulation, and MMP-13 and p-NF-κB upregulation in CHON-001 cells were notably reversed by Tanshinone I treatment. Moreover, Tanshinone I alleviated cartilage destruction and synovitis and reduced OARSI scores and subchondral bone thickness in a mouse model of OA.
Our findings showed that Tanshinone I could alleviate the progression of OA in vitro and in vivo. These results demonstrated that Tanshinone I might be regarded as a promising therapeutic agent for the treatment of OA.
骨关节炎（OA）是一种常见的退行性关节疾病，其特征为炎症和软骨降解。越来越多的证据表明丹参酮I在多种疾病中具有抗炎作用。然而，丹参酮I作为OA抗炎剂的疗效仍不清楚。本研究旨在探讨丹参酮I在体外和体内对OA的作用。
用白细胞介素-1β（IL-1β，10 ng/mL）处理CHON-001细胞72小时以在体外诱导OA模型。同时，用20 μM丹参酮I预处理CHON-001细胞24小时，然后用IL-1β（10 ng/mL）刺激72小时。分别采用CCK-8、免疫荧光和流式细胞术检测CHON-001细胞的活力、增殖和凋亡。采用蛋白质免疫印迹法检测CHON-001细胞中II型胶原蛋白、聚集蛋白聚糖、基质金属蛋白酶-13（MMP-13）、裂解的半胱天冬酶1、Gasdermin D、SOX11和磷酸化核因子κB（p-NF-κB）的水平。此外，通过右膝前交叉韧带横断术（ACLT）建立OA小鼠模型。同时，给小鼠腹腔注射10或30 mg/kg丹参酮I，持续8周。采用番红O/固绿染色评估OA小鼠模型中的软骨破坏情况。
在本研究中，IL-1β显著诱导CHON-001细胞凋亡、细胞外基质降解和炎症反应。丹参酮I显著抑制IL-1β诱导的CHON-001细胞凋亡。此外，丹参酮I处理显著逆转了IL-1β诱导的CHON-001细胞中II型胶原蛋白、聚集蛋白聚糖降解、SOX11下调以及MMP-13和p-NF-κB上调。此外，丹参酮I减轻了OA小鼠模型中的软骨破坏和滑膜炎，并降低了骨关节炎研究学会国际分会（OARSI）评分和软骨下骨厚度。
我们的研究结果表明，丹参酮I可以在体外和体内减轻OA的进展。这些结果表明，丹参酮I可能被视为一种有前景的OA治疗药物。
