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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.

cartilage

Hyperosmolar Potassium (K<sup>+</sup>) Treatment Suppresses Osteoarthritic Chondrocyte Catabolic and Inflammatory Protein Production in a 3-Dimensional <i>In Vitro</i> Model

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

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