Synovial transcriptomic signature associated with secondary arthrofibrosis of the shoulder

Background Secondary arthrofibrosis (sAF) of the shoulder is a complication after trauma or surgery characterized by stiffness, pain, and restricted mobility; however, not all injuries lead to sAF. The underlying pathophysiology of sAF is not well understood. We sought to identify key molecular mechanisms associated with the development of shoulder sAF and to identify transcriptomic differences by conducting high throughput bulk RNA sequencing (RNA-Seq) of synovial tissue from patients with sAF and from patients showing no clinical signs of sAF following shoulder trauma or surgery. Methods We assembled a cohort of 33 patients after shoulder surgery or injuries, where n = 17 developed sAF, and n = 16 did not. Arthroscopic capsular release was performed on sAF patients, while non-sAF patients underwent different shoulder procedures. Synovia was collected during surgery and subjected to bulk RNA-Seq followed by statistical and bioinformatic analyses to identify differentially expressed genes (DEGs) and associated enriched pathways. Results Transcriptomic analyses revealed a total of 173 DEGs in sAF compared to the non-sAF group, with 119 upregulated and 54 downregulated. Pathway enrichment analysis showed upregulated DEGs were enriched for signal transduction, immune system, and endocrine system pathway categories, particularly involving Epithelial-to-Mesenchymal Transition regulation, nerve growth factor (NGF)-stimulated transcription, and insulin signaling. Conclusions We identified transcriptomic differences in synovia of patients who developed sAF of the shoulder compared to patients who did not. These transcriptomic differences were associated with unique biological functions and signaling pathways that may help to understand molecular mechanisms present in patients at risk of developing sAF.