ARE METABOLOMIC PROFILES OF DEGENERATED AND NON-DEGENERATED ROTATOR CUFF TEARS IDENTICAL?

Tissue metabolomics has the potential to elucidate in situ alterations in disease pathogenesis, a knowledge gap particularly evident in the study of degenerated and non-degenerated supraspinatus (SSp) tendons. This investigation sought to characterize the metabolomic profiles of rotator cuff tears. Purpose: Rotator cuff tears (RCTs) cause loss of function and shoulder pain, with the supraspinatus (SSp) muscle being the most frequently affected. Inflammation and complex metabolic changes may play a role in the etiology of RCTs. Evaluation of metabolomic differences between the degenerate and non-degenerate SSp tissues of RCT patients were aimed. A cross-sectional study in 14 patients with RCTs based on physical examination and magnetic resonance imaging was designed. Degenerate and non-degenerate SSp tissue debris were obtained during arthroscopic surgery. Untargeted metabolomic analysis using liquid chromatography quadrupole time-of flight mass spectrometry (LC-Q-ToF-MS), was undertaken. Metabolic peaks were identified, matched and intensities were analysed after normalization. Partial least squares-discriminant analysis (PLS-DA), heatmap, unsupervised volcano plots graph and supervised fold changes were recorded. The putative metabolite lists were extracted to find the pathways of degeneration. The tyrosine metabolism, ferroptosis, steroidogenesis, lipid metabolism and cholesterol biosynthesis were altered in the degenerated RCT tissues. These findings suggest that metabolomic alterations may be associated with the development of RCTs. The observed changes in tyrosine metabolism, ferroptosis and lipid metabolism could potentially contribute to muscle degeneration and inflammation. Identified changes in steroidogenesis may provide new insights into the role of hormonal factors in RCT development. Clinical Relevance: Understanding the metabolic pathways of tyrosine metabolism, ferroptosis, steroidogenesis, and lipid metabolism in rotator cuff tears is clinically relevant in sports medicine as it enables targeted therapies and personalized treatment strategies, enhancing recovery and improving outcomes for athletes. Level of Evidence of the Study: Level II prognostic study