Integrated transcriptomic and metabolomic analysis reveals arginine-citrulline gene-compound network is critical for severe adhesive capsulitis progression

Adhesive capsulitis (AC) affects 2–5% of the population worldwide. Patients with severe AC fail to regain a complete range of movement and experience years of shoulder pain. Unfortunately, the underlying mechanism of severe AC remains unclear. Here, we performed an integrated transcriptomic and metabolomic data analysis of serum and tissue samples from patients with severe AC, mild AC, and healthy controls. Pathways related to muscle development and myogenesis positively correlated with severe AC progression. Further, we identified an arginine-citrulline gene-compound network that may play a central role in severe AC. Comparing differentially regulated metabolites from tissue and serum, two phospholipids were recognized as potential serum markers for severe AC. In conclusion, this is the first comprehensive integrated -omics study on severe AC and provides insights into genes and compounds of the arginine-citrulline metabolic pathway that may be potential therapeutic targets for treating AC. Overall design: We collected tissues and serum from patients with 13 severe and 12 mild AC and 5 healthy controls. We randomly selected 4 patients from each group and sequenced their proliferative synovium and joint capsule tissues.