Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Medicinal and Natural Chemistry Rresearch Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Iran J Med Sci. 2021 Sep;46(5):383-394. doi: 10.30476/IJMS.2020.83686.1301.
Osteoarthritis (OA) is a degenerative joint disease that causes a variety of adverse health effects. Considering the need to identify additional effective therapeutic options for OA therapy, we investigated the effect of co-injection of apigenin and synovial membrane-derived mesenchymal stem cells (SMMSCs) on OA in male rats' knee joints.
The study was performed in 2019 at the Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. Anterior cruciate ligament transection (ACLT) was used to induce OA. For three weeks, male Sprague-Dawley rats (eight groups, n=6 each) were treated once-weekly with intra-articular injections of apigenin alone or in combination with SMMSC (three million cells), phosphate-buffered saline, or hyaluronic acid. After three months, the interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the cartilage homogenate. The expression of extracellular matrix (ECM) components including collagen 2a1, aggrecan, IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), transcription factor SOX-9, and matrix metalloproteinases 3 and 13 were assessed using real-time polymerase chain reaction (RT-PCR) analysis. Radiological evaluation and histopathological assessment were used to evaluate the knees.
Levels of TNF-α (P=0.009), MDA (P>0.001), and IL-1β (P<0.001) decreased and the level of SOD increased (P=0.004) in the apigenin 0.3 µM with SMMSCs group. RT-PCR analysis indicated that IL-1β in the apigenin 0.3 µM with SMMSCs group reduced significantly (P<0.001). This group also exhibited increased expression levels of SOX-9, collagen 2a1, and aggrecan (P<0.001).
Apigenin may have supplementary beneficial effects on cell therapy in a rat model of OA due to its possible effect on the reduction of oxidative stress, suppression of inflammation, and promotion of production of ECM components.
骨关节炎（OA）是一种退行性关节疾病，会导致多种不良健康影响。鉴于需要为 OA 治疗确定其他有效治疗选择，我们研究了芹菜素和滑膜间充质干细胞（SMMSC）共同注射对雄性大鼠膝关节 OA 的影响。
该研究于 2019 年在伊朗 Shiraz 大学医学院药理学系进行。前交叉韧带切断术（ACLT）用于诱导 OA。在三周内，雄性 Sprague-Dawley 大鼠（8 组，每组 6 只）每周一次接受关节内注射单独的芹菜素或与 SMMSC（三百万个细胞）、磷酸盐缓冲盐水或透明质酸联合治疗。三个月后，测量软骨匀浆中的白细胞介素 1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、超氧化物歧化酶（SOD）和丙二醛（MDA）水平。使用实时聚合酶链反应（RT-PCR）分析评估细胞外基质（ECM）成分的表达，包括胶原 2a1、聚集蛋白聚糖、IL-1β、TNF-α、诱导型一氧化氮合酶（iNOS）、转录因子 SOX-9 和基质金属蛋白酶 3 和 13。使用放射学评估和组织病理学评估来评估膝关节。
在芹菜素 0.3 µM 与 SMMSC 组中，TNF-α（P=0.009）、MDA（P>0.001）和 IL-1β（P<0.001）水平降低，SOD 水平升高（P=0.004）。RT-PCR 分析表明，芹菜素 0.3 µM 与 SMMSC 组中 IL-1β 显著降低（P<0.001）。该组还表现出 SOX-9、胶原 2a1 和聚集蛋白聚糖表达水平升高（P<0.001）。
由于芹菜素可能通过降低氧化应激、抑制炎症和促进 ECM 成分的产生对细胞治疗产生补充的有益作用，因此它可能对 OA 大鼠模型中的细胞治疗具有辅助有益作用。
