Department of Biomedical Engineering, Rensselaer Polytechnic Institute (RPI), Troy, NY, USA.
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute (RPI), Troy, NY, USA.
Cartilage. 2021 Dec;13(2_suppl):713S-721S. doi: 10.1177/1947603520961167. Epub 2020 Sep 25.
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.
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.
TNF-α treatment increased sGAG loss ( < 0.001) and expression of COX-2 ( = 0.018), MMP-13 ( < 0.001), and VEGF ( = 0.017) relative to unstimulated controls. Relative to activated controls, LiCl and dexamethasone treatment attenuated sGAG loss ( = 0.008 and = 0.042, respectively) and expression of MMP-13 ( = 0.005 and = 0.036, respectively). In contrast, KCl treatment exacerbated sGAG loss ( = 0.032) and MMP-1 protein expression ( = 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 ( < 0.05) in catabolic and inflammatory mediators following LiCl treatment.
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.
本研究旨在比较高渗钠（Na）、锂（Li）和钾（K）对肿瘤坏死因子-α（TNF-α）刺激软骨外植体中分解代谢和炎症性骨关节炎（OA）标志物及硫酸化糖胺聚糖（sGAG）丢失的影响。
用 TNF-α刺激牛膝关节软骨外植体 1 天，诱导软骨降解，然后再用 50 mM 氯化钾（KCl）、50 mM 氯化锂（LiCl）、50 mM 氯化钠（NaCl）或 100 nM 地塞米松处理 6 天。我们评估了 TNF-α刺激和高渗离子处理对 sGAG 丢失和 OA 相关蛋白表达的影响：ADAMTS-5、COX-2、MMP-1、MMP-13 和 VEGF。
与未刺激对照组相比，TNF-α处理增加了 sGAG 丢失（<0.001）和 COX-2（=0.018）、MMP-13（<0.001）和 VEGF（=0.017）的表达。与激活对照组相比，LiCl 和地塞米松处理减轻了 sGAG 丢失（=0.008 和=0.042，分别）和 MMP-13 的表达（=0.005 和=0.036，分别）。相反，KCl 处理加剧了 sGAG 丢失（=0.032）和 MMP-1 蛋白表达（=0.010）。然而，NaCl 处理并没有改变 sGAG 丢失或 OA 相关蛋白的表达。比较 LiCl 和 KCl 处理表明，LiCl 处理后，分解代谢和炎症介质的减少具有明显的作用（<0.05）。
这些结果表明，这些离子种类在 TNF-α刺激的外植体中产生不同的反应。综上所述，这些发现支持进一步研究高渗离子溶液，以开发针对 OA 的新型关节内注射。
