MicroRNAs associated with inflammation in shoulder tendinopathy and glenohumeral arthritis.

Inflammation is associated with glenohumeral arthritis and rotator cuff tendon tears. Epigenetically, miRNAs tightly regulate various genes involved in the inflammatory response. Alterations in the expression profile of miRNAs and the elucidation of their target genes with respect to the pathophysiology could improve the understanding of their regulatory role and therapeutic potential. Here, we screened key miRNAs that mediate inflammation and linked with JAK2/STAT3 pathway with respect to the coincidence of glenohumeral arthritis in patients suffering from rotator cuff injury (RCI). Human resected long head of the biceps tendons were examined for miRNA profile from two groups of patients: Group 1 included the patients with glenohumeral arthritis and massive rotator cuff tears and the Group 2 patients did not have arthritis or rotator cuff tears. The miRNA profiling revealed that 235 miRNAs were highly altered (fold change less than -3 and greater than +2 were considered). Data from the NetworkAnalyst program revealed the involvement and interaction between 3,430 different genes associated with inflammation out of which 284 genes were associated with JAK2/STAT3 pathway and interconnect 120 different pathways of inflammation. Around 1,500 miRNAs were found to play regulatory role associated with these genes of inflammatory responses and 77 miRNAs were found to regulate more than 10 genes. Among them, 25 genes with less than tenfold change were taken to consideration which altogether constitute for the regulation of 102 genes. Targeting these miRNAs and the underlying regulatory mechanisms may advance our knowledge to develop promising therapies in the management of shoulder tendon pathology.