Expression of Apelin in Rotator Cuff Tears and Examination of Its Regulatory Mechanism: A Translational Study

Objectives: Inflammatory mediators play important roles in the pain associated with rotator cuff tears (RCTs), but their underlying mechanisms are unclear. Apelin, a neuropeptide, is upregulated under inflammatory conditions and possibly contributes to pain induced by rotator cuff tears. This translational study aimed to examine apelin expression and regulation by tumor necrosis factor alpha (TNF-α) in patients with RCT and in rat RCT models. Methods: Synovial tissues were harvested from the glenohumeral joints of the shoulders in 46 patients who underwent arthroscopic Bankart repair for recurrent shoulder dislocations (RSDs) or arthroscopic rotator cuff repair for RCTs. The harvested tissues were extracted and processed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rats underwent sham or RCT surgery; the rotator cuff tissues were extracted 1, 7, 14, 28, and 56 days after surgery and analyzed for mRNA expression levels of the TNF-α and apelin using RT-PCR. The cultured rotator cuff cells (RCCs) were stimulated with TNF-α to examine their role in the regulation of apelin expression. Results: Apelin expression was higher in the RCT group than in the RSD group and significantly correlated with pain intensity. In rats, the expression was also higher in RCT. Apelin expression significantly increased during the acute and chronic phases in rats. Conclusions: In cultured RCCs, apelin mRNA levels significantly increased after TNF-α stimulation. Apelin levels were regulated by TNF-α and were highly expressed in patients with RCT and rats in RCT models. Thus, apelin may be a new pain management target for RCTs.