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

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.