Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok, Poland.
Faculty of Chemistry, University in Bialystok, K. Ciołkowskiego 1K, 15-245 Bialystok, Poland.
Molecules. 2021 Feb 7;26(4):878. doi: 10.3390/molecules26040878.
Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1β (IL-1β) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1β, as shown by down regulation of , , and , and increased the expression of antioxidant enzyme . Additionally, TUDCA enhanced expression in IL-1β- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.
骨关节炎（OA）被认为是最常见的关节炎疾病之一，其特征是关节软骨进行性退化和异常重塑。OA 的潜在治疗方法旨在恢复适当的软骨细胞功能并抑制细胞凋亡。先前的研究表明，牛磺熊脱氧胆酸（TUDCA）在许多不同疾病的模型中表现出抗炎和抗细胞凋亡活性，主要通过缓解内质网（ER）应激起作用。然而，关于 TUDCA 对软骨细胞的细胞保护作用知之甚少。本研究旨在评估 TUDCA 对在常氧和低氧条件下培养的白细胞介素 1β（IL-1β）和衣霉素（TNC）刺激的 NHAC-kn 软骨细胞的潜在影响。我们的结果表明，TUDCA 通过降低 CHOP 表达减轻 TNC 处理的软骨细胞中的 ER 应激；然而，它在常氧或低氧条件下均不足以预防 NHAC-kn 细胞的凋亡。然而，TUDCA 与 TUDCA 联合治疗减轻了由 IL-1β诱导的炎症反应，表现为下调 、 、 和 ，并增加抗氧化酶 的表达 。此外，TUDCA 增强了在 IL-1β和 TNC 刺激的细胞中的 表达，但仅在常氧条件下。总之，这些结果表明，尽管 TUDCA 可能在 ER 应激细胞中显示出软骨保护潜力，但仍需要进一步分析才能完全确认其作为 OA 治疗潜在候选药物的可能推荐。
