Tissue-specific and spatially dependent metabolic signatures perturbed by injury in male and female mice.

Joint injury induces coordinated metabolic responses locally and systemically that extend beyond the injured joint and are influenced by sex. Integrating metabolomic and spatial analyses reveals how injury modulates joint pathophysiology across tissues and reveals sex-specific patterns relevant to PTOA risk. These findings improve pre-clinical PTOA models and deepen our understanding of the complex role of injury and sex in osteoarthritis pathogenesis, laying the foundation for targeted therapeutic strategies.