Abstract
Injury is a risk factor for post-traumatic osteoarthritis (PTOA). However, metabolic and microarchitectural changes within the joint post-injury in both sexes remain unexplored. This study identified tissue-specific and spatially-dependent metabolic signatures in male and female mice using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and metabolomics. Male and female C57Bl/6J mice were subjected to non-invasive joint injury. Eight days post-injury, serum, synovial fluid, and whole joints were collected for metabolomics to compare samples from injured, contralateral, and naïve mice, revealing local and systemic responses. Results indicate sex influences metabolic profiles across all tissues, particularly amino acid, purine, and pyrimidine metabolism. MALDI-MSI generated 2D ion images of bone, growth plate, and marrow, revealing increased lipid species in injured limbs, suggesting metabolic shifts across injured joints at metabolic and spatial levels. Together, these findings reveal significant metabolic changes after injury, with notable sex differences.
Competing Interest Statement
Authors have no conflicts of interest to disclose. Dr. June owns stock in Beartooth Biotech and OpenBioWorks, which were not involved in this study.