1 Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
Cartilage. 2019 Apr;10(2):186-195. doi: 10.1177/1947603517734028. Epub 2017 Oct 9.
The main goal of this study was to provide a proof-of-concept demonstrating that hyperosmolar K solutions can limit production of catabolic and inflammatory mediators in human osteoarthritic chondrocytes (OACs).
A 3-dimensional in vitro model with poly(ethylene glycol) diacrylate (PEGDA) hydrogels was used. Catabolic and pro-inflammatory protein production from encapsulated OACs was assessed following culture for 1 or 7 days in the presence or absence of 80 mM K gluconate, 80 mM sodium (Na) gluconate, or 160 mM sucrose, each added to culture media (final osmolarity ~490 mOsm).
Relative to untreated controls, OACs treated with hyperosmolar (80 mM Na gluconate or 160 mM sucrose) solutions produced lower levels of catabolic and inflammatory mediators in a marker- and time-dependent manner (i.e., MMP-9 after 1 day; MCP-1 after 7 days ( P ≤ 0.015)). In contrast, OAC treatment with 80 mM K gluconate reduced catabolic and inflammatory mediators to a greater extent (both the number of markers and degree of suppression) relative to untreated, Na gluconate, or sucrose controls (i.e., MMP-3, -9, -13, TIMP-1, MCP-1, and IL-8 after 1 day; MMP-1, -3, -9, -13, TIMP-1, MCP-1, and IL-8 after 7 days ( P ≤ 0.029).
Hyperosmolar K solutions are capable of attenuating protein production of catabolic and inflammatory OA markers, providing the proof-of-concept needed for further development of a K-based intra-articular injection for OA treatment. Moreover, K performed significantly better than Na- or sucrose-based solutions, supporting the application of K toward improving irrigation solutions for joint surgery.
本研究的主要目的是提供一个概念验证,证明高渗 K 溶液可以限制人骨性关节炎软骨细胞(OAC)中分解代谢和炎症介质的产生。
使用聚乙二醇二丙烯酸酯(PEGDA)水凝胶的 3 维体外模型。在存在或不存在 80 mM K 葡萄糖酸盐、80 mM 葡萄糖酸钠或 160 mM 蔗糖的情况下,培养 1 或 7 天,评估包封的 OAC 产生的分解代谢和促炎蛋白。将每种物质添加到培养基中(终渗透压约为 490 mOsm)。
与未处理的对照相比,高渗(80 mM 葡萄糖酸钠或 160 mM 蔗糖)溶液处理的 OAC 以标记物和时间依赖性的方式产生较低水平的分解代谢和炎症介质(即,MMP-9 在 1 天后;MCP-1 在 7 天后(P≤0.015))。相比之下,80 mM K 葡萄糖酸盐处理相对于未处理、葡萄糖酸钠或蔗糖对照更显著地降低了分解代谢和炎症介质(即,MMP-3、-9、-13、TIMP-1、MCP-1 和 IL-8 在 1 天后;MMP-1、-3、-9、-13、TIMP-1、MCP-1 和 IL-8 在 7 天后(P≤0.029))。
高渗 K 溶液能够减弱分解代谢和炎症性 OA 标志物的蛋白产生,为进一步开发用于 OA 治疗的基于 K 的关节内注射提供了概念验证。此外,K 的效果明显优于基于 Na 或蔗糖的溶液,支持将 K 应用于改善关节手术的灌洗溶液。