Steinecker-Frohnwieser Bibiane, Kaltenegger Heike, Weigl Lukas, Mann Anda, Kullich Werner, Leithner Andreas, Lohberger Birgit
Ludwig Boltzmann Department for Rehabilitation of Internal Diseases, Ludwig Boltzmann Cluster for Arthritis and Rehabilitation, Thorerstrasse 26, 5760 Saalfelden, Austria.
Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
Biochem Biophys Rep. 2017 Jul 1;11:154-160. doi: 10.1016/j.bbrep.2017.06.006. eCollection 2017 Sep.
Osteoarthritis (OA) as the main chronic joint disease arises from a disturbed balance between anabolic and catabolic processes leading to destructions of articular cartilage of the joints. While mechanical stress can be disastrous for the metabolism of chondrocytes, mechanical stimulation at the physiological level is known to improve cell function. The disease modifying OA drug (DMOAD) diacerein functions as a slowly-acting drug in OA by exhibiting anti-inflammatory, anti-catabolic, and pro-anabolic properties on cartilage. Combining these two treatment options revealed positive effects on OA-chondrocytes.
Cells were grown on flexible silicone membranes and mechanically stimulated by cyclic tensile loading. After seven days in the presence or absence of diacerein, inflammation markers and growth factors were analyzed using quantitative real-time PCR and enzyme linked immune assays. The influence of conditioned medium was tested on cell proliferation and cell migration.
Tensile strain and diacerein treatment reduced interleukin-6 (IL-6) expression, whereas cyclooxygenase-2 (COX2) expression was increased only by mechanical stimulation. The basic fibroblast growth factor (bFGF) was down regulated by the combined treatment modalities, whereas prostaglandin E2 (PGE2) synthesis was reduced only under OA conditions. The expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor A (VEGF-A) was down-regulated by both.
From our study we conclude that moderate mechanical stimulation appears beneficial for the fate of the cell and improves the pharmacological effect of diacerein based on cross-talks between different initiated pathways.
Combining two different treatment options broadens the perspective to treat OA and improves chondrocytes metabolism.
骨关节炎（OA）作为主要的慢性关节疾病，是由合成代谢和分解代谢过程之间的平衡失调引起的，导致关节软骨破坏。虽然机械应力对软骨细胞的代谢可能是灾难性的，但生理水平的机械刺激已知可改善细胞功能。改善病情的骨关节炎药物（DMOAD）双醋瑞因在OA中作为一种慢效药物，通过对软骨表现出抗炎、抗分解代谢和促合成代谢特性发挥作用。将这两种治疗方法结合起来对OA软骨细胞显示出积极效果。
细胞在柔性硅胶膜上生长，并通过循环拉伸加载进行机械刺激。在存在或不存在双醋瑞因的情况下培养7天后，使用定量实时PCR和酶联免疫测定法分析炎症标志物和生长因子。测试条件培养基对细胞增殖和细胞迁移的影响。
拉伸应变和双醋瑞因处理降低了白细胞介素-6（IL-6）的表达，而环氧合酶-2（COX2）的表达仅通过机械刺激增加。联合治疗方式下调了碱性成纤维细胞生长因子（bFGF），而仅在OA条件下前列腺素E2（PGE2）的合成减少。血小板衍生生长因子（PDGF）和血管内皮生长因子A（VEGF-A）的表达均被下调。
从我们的研究中得出结论，适度的机械刺激似乎对细胞命运有益，并基于不同起始途径之间的相互作用改善双醋瑞因的药理作用。
结合两种不同的治疗方法拓宽了治疗OA的视野，并改善软骨细胞代谢。
