When aiming at cell‐based therapies in osteoarthritis (OA), proinflammatory conditions mediated by cytokines such as IL‐1β need to be considered. In recent studies, the phytoalexin resveratrol (RSV) has exhibited potent anti‐inflammatory properties. However, long‐term effects on 3D cartilaginous constructs under inflammatory conditions with regard to tissue quality, especially extracellular matrix (ECM) composition, have remained unexplored. Therefore, we employed long‐term model cultures for cell‐based therapies in an in vitro OA environment and evaluated effects of RSV. Pellet constructs made from expanded porcine articular chondrocytes were cultured with either IL‐1β (1–10 ng/ml) or RSV (50 μM) alone, or a cotreatment with both agents. Treatments were applied for 14 days, either directly after pellet formation or after a preculture period of 7 days. Culture with IL‐1β (10 ng/ml) decreased pellet size and DNA amount and severely compromised glycosaminoglycan (GAG) and collagen content. Cotreatment with RSV distinctly counteracted the proinflammatory catabolism and led to partial rescue of the ECM composition in both culture systems, with especially strong effects on GAG. Marked MMP13 expression was detected in IL‐1β‐treated pellets, but none upon RSV cotreatment. Expression of collagen type I was increased upon IL‐1β treatment and still observed when adding RSV, whereas collagen type X, indicating hypertrophy, was detected exclusively in pellets treated with RSV alone. In conclusion, RSV can counteract IL‐1β‐mediated degradation and distinctly improve cartilaginous ECM deposition in 3D long‐term inflammatory cultures. Nevertheless, potential hypertrophic effects should be taken into account when considering RSV as cotreatment for articular cartilage repair techniques.

中文翻译：

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白藜芦醇抵消 IL-1β 介导的 3D 关节软骨细胞构建体中细胞外基质沉积的损害。

当针对骨关节炎 (OA) 的细胞疗法时，需要考虑由细胞因子如 IL-1β 介导的促炎条件。在最近的研究中，植物抗毒素白藜芦醇 (RSV) 表现出强大的抗炎特性。然而，在炎症条件下对 3D 软骨结构在组织质量方面的长期影响，尤其是细胞外基质 (ECM) 组成，仍未得到探索。因此，我们在体外 OA 环境中采用了基于细胞疗法的长期模型培养物，并评估了 RSV 的效果。由扩增的猪关节软骨细胞制成的颗粒构建体与单独的 IL-1β (1-10 ng/ml) 或 RSV (50 μM) 一起培养，或与这两种药剂共同处理。治疗持续 14 天，直接在颗粒形成后或在 7 天的预培养期后。用 IL-1β (10 ng/ml) 培养会降低颗粒大小和 DNA 量，并严重影响糖胺聚糖 (GAG) 和胶原蛋白含量。与 RSV 共同治疗明显抵消了促炎分解代谢，并导致两种培养系统中 ECM 成分的部分挽救，对 GAG 的影响尤其强烈。在 IL-1β 处理的颗粒中检测到显着的 MMP13 表达，但在 RSV 共处理时没有检测到。I 型胶原蛋白的表达在 IL-1β 处理后增加，并且在加入 RSV 时仍然观察到，而 X 型胶原蛋白，表明肥大，仅在单独用 RSV 处理的颗粒中检测到。综上所述，RSV 可以抵消 IL-1β 介导的降解，并显着改善 3D 长期炎症培养中的软骨 ECM 沉积。然而，在考虑 RSV 作为关节软骨修复技术的联合治疗时，应考虑潜在的肥大效应。