Fibronectin Enhances Cartilage Repair by Activating Progenitor Cells Through Integrin 51 Receptor

This study aimed to determine the effect of fibronectin (FN) on cartilage regeneration through the activation of chondrogenic progenitor cells (CPCs). Cells were isolated from the knee cartilage of mice and cultured in the presence of various concentrations of FN. Proliferation, migration, and chondrogenic differentiation assays were performed in vitro. In some experiments, CPCs were preincubated with anti-integrin 51 antibody for 60min before FN treatment to block the integrin 51 receptor. Soluble FN was mixed with Pluronic F-127 and injected into the joint cavity in an early-stage osteoarthritis model. Cartilage repair was evaluated histologically, biochemically, and biomechanically. In vitro, we observed that the isolated CPCs, which exhibited stem cell-relevant markers, proliferated most at a concentration of 20g/mL FN (p<0.05). In addition, FN enhanced the proliferation, migration, and chondrogenic differentiation capacity of CPCs, and the enhancement was significantly decreased by blockade of the integrin 51 receptor (p<0.05). In vivo, FN also significantly promoted cartilage repair along with increased CPC activation and integrin 51 expression (p<0.05). These findings suggest that FN enhances CPC proliferation, migration, and chondrogenic differentiation through the integrin 51-dependent signaling pathway. Based on these results, a novel and promising therapy focused on targeted activation of CPCs by FN could be developed for the treatment of cartilage injuries in a clinical setting.