Objective

The objective of this study was to compare the effects of hyperosmolar sodium (Na⁺), lithium (Li⁺) and potassium (K⁺) on catabolic and inflammatory osteoarthritis (OA) markers and sulfated glycosaminoglycan (sGAG) loss in TNF-α-stimulated cartilage explants.

Methods

Explants from bovine stifle joints were stimulated with TNF-α for 1 day to induce cartilage degradation followed by supplementation with 50 mM potassium chloride (KCl), 50 mM lithium chloride (LiCl), 50 mM sodium chloride (NaCl), or 100 nM dexamethasone for an additional 6 days. We assessed the effect of TNF-α stimulation and hyperosmolar ionic treatment on sGAG loss and expression of OA-associated proteins: ADAMTS-5, COX-2, MMP-1, MMP-13, and VEGF.

Results

TNF-α treatment increased sGAG loss (P < 0.001) and expression of COX-2 (P = 0.018), MMP-13 (P < 0.001), and VEGF (P = 0.017) relative to unstimulated controls. Relative to activated controls, LiCl and dexamethasone treatment attenuated sGAG loss (P = 0.008 and P = 0.042, respectively) and expression of MMP-13 (P = 0.005 and P = 0.036, respectively). In contrast, KCl treatment exacerbated sGAG loss (P = 0.032) and MMP-1 protein expression (P = 0.010). NaCl treatment, however, did not alter sGAG loss or expression of OA-related proteins. Comparing LiCl and KCl treatment shows a potent reduction (P < 0.05) in catabolic and inflammatory mediators following LiCl treatment.

Conclusion

These results suggest that these ionic species elicit varying responses in TNF-α-stimulated explants. Cumulatively, these findings support additional studies of hyperosmolar ionic solutions for potential development of novel intraarticular injections targeting OA.

中文翻译：

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高渗离子溶液调节软骨外植体模型中的炎症表型和 sGAG 损失。

客观的

本研究的目的是比较高渗钠 (Na ⁺ )、锂 (Li ⁺ ) 和钾 (K ⁺ ) 对分解代谢和炎症性骨关节炎 (OA) 标志物以及 TNF-α- 中硫酸化糖胺聚糖 (sGAG) 损失的影响刺激软骨外植体。

方法

用 TNF-α 刺激牛膝关节外植体 1 天，诱导软骨降解，然后补充 50 mM 氯化钾 (KCl)、50 mM 氯化锂 (LiCl)、50 mM 氯化钠 (NaCl) 或 100 nM 地塞米松额外 6 天。我们评估了 TNF-α 刺激和高渗离子治疗对 sGAG 损失和 OA 相关蛋白（ADAMTS-5、COX-2、MMP-1、MMP-13 和 VEGF）表达的影响。

结果

与未刺激对照相比，TNF-α 治疗增加了 sGAG 损失（P < 0.001）以及 COX-2（ P = 0.018）、MMP-13（P < 0.001）和 VEGF（P = 0.017）的表达。相对于激活对照，LiCl和地塞米松治疗减弱了 sGAG 损失（分别为P = 0.008 和P = 0.042）和 MMP-13 表达（分别为P = 0.005 和P = 0.036）。相反，KCl 处理加剧了 sGAG 损失（P = 0.032）和 MMP-1 蛋白表达（P = 0.010）。然而，氯化钠处理并没有改变 sGAG 的丢失或 OA 相关蛋白的表达。比较 LiCl 和 KCl 治疗表明，LiCl 治疗后分解代谢和炎症介质显着减少 ( P < 0.05)。

结论

这些结果表明这些离子种类在 TNF-α 刺激的外植体中引起不同的反应。总的来说，这些发现支持了对高渗离子溶液的进一步研究，以开发针对 OA 的新型关节内注射剂。