The effect of kaempferol and apigenin on allogenic synovial membrane-derived stem cells therapy in knee osteoarthritic male rats
The effect of kaempferol and apigenin on allogenic synovial membrane-derived stem cells therapy in knee osteoarthritic male rats
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DOI：
10.1016/j.knee.2020.03.005
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发表时间：
2020-06-01
期刊：
影响因子：
1.9
通讯作者：
Gholijani, Nasser
中科院分区：
文献类型：
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作者：
Estakhri, Firoozeh;Panjehshahin, Mohammad Reza;Gholijani, Nasser
背景：基于山奈酚和芹菜素的抗炎和抗氧化特性，我们假设联合注射这些植物化学物质可以提高膝关节骨关节炎大鼠的细胞治疗效果。方法：采用前交叉韧带横断术（ACLT）诱导骨关节炎（OA）。动物每周关节内注射山奈酚（10或20 μ M）和/或从滑膜（SMMSCs）分离的间充质干细胞（3 × 106个细胞），芹菜素（0.1 μ M）和山奈酚单独或SMMSCs、透明质酸或PBS（组数n 6）的混合物，持续三周。3个月后，测定软骨匀浆中IL-1 β、肿瘤坏死因子α (tnf - α)、超氧化物歧化酶（SOD）和丙二醛（MDA）的水平。此外，采用实时荧光定量PCR检测胶原蛋白II2a1、聚集蛋白、IL-1 β、tnf - α、诱导型一氧化氮合酶（iNOS）、SOX-9、MMP-3和MMP-13的相对表达。通过放射学评估、治疗前后和组织病理学评估对膝关节进行评估。结果：山奈酚和芹菜素的无毒浓度分别为10、20 μ M和0.1、03 μ M。与OA组比较，OA MSCs +山奈酚+芹菜素组tnf - α、IL-1 β、MDA水平显著降低，SOD水平显著升高。OA + MSCs + A0.1 μ M + K10 μ M和OA + MSCs K20 μ M组MMP-13、MMP-3、tnf - α、IL-1 β、iNOS水平均显著降低，山奈普酚和芹菜素共处理可提高胶原11a1、聚集蛋白和SOX-9基因的表达水平。结论：山奈酚和芹菜素在aclt诱导的OA大鼠模型中可能提高OA细胞治疗的效率。(C) 2020 Elsevier B.V.版权所有
Background: Based on the anti-inflammatory and anti-oxidant properties of kaempferol and apigenin, we hypothesized that co-injection of these phytochcmicals would increase the effectiveness of cell therapy in knee osteoarthritic rats.Methods: Anterior crutiate ligament transection (ACLT) was used to induce osteoarthritis (OA). Animals were treated by weekly intra-articular injections of kaempferol (10 or 20 mu M) and/or isolated MSCs from synovial membrane (SMMSCs) (3 x 106 cells), a mixture of apigenin (0.1 mu M) and kaempferol alone or SMMSCs, hyaluronic acid or PBS (group size n 6), for three weeks. After three months, the levels of IL-1 beta, tumor necrosis factor alpha (TNF-alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in the cartilage homogenate. Furthermore, relative expressions of collagen II2a1, aggrecan, IL-1 beta, TNF-alpha, inducible nitric oxide synthase (iNOS), SOX-9, MMP-3 and MMP-13 were assessed using real-time PCR. Radiological evaluation, before/after treatments, and histopathological assessments were carried out to evaluate the knees.Results: Non-toxic concentrations of kaempferol and apigenin determined to be 10, 20 mu M and 0.1, 03 mu M, respectively. In comparison with the OA group, the levels of TNF-alpha, IL-1 beta and MDA significantly decreased in OA MSCs + kaempferol + apigenin group and a significant in- crease in SOD level was observed. The levels of MMP-13, MMP-3, TNF-alpha, IL-1 beta, iNOS were significantly decreased in the groups of OA + MSCs + A0.1 mu M + K10 mu M and OA + MSCs K20 mu M. Co-treatment of kaempferol and apigenin increased the gene expression levels of collagen 11a1, aggrecan and SOX-9 genes.Conclusion: We showed that kaempferol and apigenin potentially increase the efficiency of OA cell therapy in the rat model of ACLT-induced OA. (C) 2020 Elsevier B.V. All rights reserved.