Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany.
Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, University of Regensburg, 93053 Regensburg, Germany.
Int J Mol Sci. 2019 Jan 30;20(3):585. doi: 10.3390/ijms20030585.
Osteoarthritis (OA) affects the integrity of the entire joint including the synovium. The most abundant cells in the synovium are fibroblasts (SF). Excessive mechanical loading might contribute to OA pathogenesis. Here, we investigate the effects of mechanical loading on SF derived from non-OA (N-SF) and OA patients (OA-SF). We treated N-SF and OA-SF with or without mechanical loading for 48h after 24h of preincubation. Then we assessed gene and protein expression of proinflammatory factors (TNFα, COX-2, PG-E2, IL-6), extracellular matrix (ECM) components (COL1, FN1) and glycosaminoglycans (GAGs) via RT-qPCR, ELISA, DMMB assay and HPLC. Mechanical loading significantly increased TNFα and PG-E2 secretion by N-SF and OA-SF, whereas in OA-SF IL-6 secretion was reduced. COL1 and FN1 secretion were downregulated in N-SF during loading. OA-SF secreted less COL1 compared to N-SF under control conditions. In contrast, OA-SF in general expressed more FN1. GAG synthesis was upregulated in N-SF, but not in OA-SF during loading with OA-SF displaying a higher charge density than N-SF. Mechanical loading enhanced proinflammatory factor expression and GAG synthesis and decreased secretion of ECM components in N-SFs, indicating a contributing role of SF to OA development.
骨关节炎（OA）会影响整个关节的完整性，包括滑膜。滑膜中最丰富的细胞是成纤维细胞（SF）。过度的机械负荷可能导致 OA 的发病机制。在这里，我们研究了机械负荷对非 OA（N-SF）和 OA 患者（OA-SF）来源的 SF 的影响。在预孵育 24 小时后，我们用或不用机械负荷处理 N-SF 和 OA-SF 48 小时。然后，我们通过 RT-qPCR、ELISA、DMMB 测定和 HPLC 评估促炎因子（TNFα、COX-2、PG-E2、IL-6）、细胞外基质（ECM）成分（COL1、FN1）和糖胺聚糖（GAGs）的基因和蛋白表达。机械负荷显著增加了 N-SF 和 OA-SF 的 TNFα 和 PG-E2 分泌，而 OA-SF 的 IL-6 分泌减少。加载过程中 N-SF 的 COL1 和 FN1 分泌下调。在对照条件下，与 N-SF 相比，OA-SF 分泌的 COL1 较少。相比之下，OA-SF 通常表达更多的 FN1。在加载过程中，N-SF 的 GAG 合成上调，但 OA-SF 中没有，OA-SF 显示出比 N-SF 更高的电荷密度。机械负荷增强了 N-SFs 中促炎因子的表达和 GAG 的合成，并减少了 ECM 成分的分泌，表明 SF 对 OA 发展有促进作用。
