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高渗钾(K)治疗在三维体外模型中抑制骨关节炎软骨细胞的分解代谢和炎症蛋白产生。

Hyperosmolar Potassium (K) Treatment Suppresses Osteoarthritic Chondrocyte Catabolic and Inflammatory Protein Production in a 3-Dimensional In Vitro Model.

机构信息

1 Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.

出版信息

Cartilage. 2019 Apr;10(2):186-195. doi: 10.1177/1947603517734028. Epub 2017 Oct 9.

Abstract

OBJECTIVE

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).

METHODS

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).

RESULTS

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).

CONCLUSIONS

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.

摘要

目的

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。

方法

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)。

结果

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))。

结论

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。

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