Epigallocatechin-3-gallate Suppresses Pain-related and Proinflammatory Mediators in the Subacromial Bursa in Rotator Cuff Tendinopathy

Rotator cuff tendinopathy is one of the leading causes of shoulder pain. However, the mechanisms involved in the development of rotator cuff tendinopathy pain are not fully understood. In this study, we first examined the histological features of subacromial bursa from patients with rotator cuff tendinopathy who had symptoms of pain, and investigated the expression of pain mediators, proinflammatory cytokines, metalloproteinases, growth factors, and alarmins in diseased tendon and bursa tissue by real-time PCR, western blot, and/or immunohistochemistry/immunofluorescence staining. Then we investigated whether epigallocatechin-3-gallate (EGCG) could reduce the expression of pain mediators and proinflammatory cytokines in human primary bursa cells and explored the paracrine effect of these EGCG-treated bursa cells on tenocytes in vitro. Neovascularization and infiltration of immune cells including monocytes/macrophages and mast cells were observed in diseased bursa tissue. Bursa from patients with pain had higher mRNA expression of pain mediators and proinflammatory cytokines, compared to the rotator cuff tendon of the same patients, as well as the bursa from asymptomatic patients. EGCG treatment significantly suppressed the interleukin 1 beta (IL-1 beta)-induced elevation of mRNA expression of pain mediators, proinflammatory cytokines, and matrix metalloproteinases (MMPs) in bursa cells in vitro; conditioned medium from EGCG-treated bursa cells significantly reduced IL-1 beta-induced expression in human primary tenocytes. Our study suggests that the subacromial bursa might serve as a local source of pain mediators and proinflammatory cytokines in rotator cuff tendinopathy. Moreover, EGCG treatment by primarily targeting the subacromial bursa may be a potential strategy to relieve rotator cuff tendinopathy-related pain and symptoms.