Feng Haotian, He Zhiyong, Twomey Kristin, Ilaltdinov Angela Wang, Leong Daniel, Wang Yanhua, Li Jianmin, Gonzalez David, Sun Hui B
Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, China.
Department of Orthopaedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Discov Med. 2019 Feb;27(147):63-77.
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-1β)-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-1β-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.
肩袖肌腱病是肩部疼痛的主要原因之一。然而，肩袖肌腱病疼痛发生发展所涉及的机制尚未完全明确。在本研究中，我们首先检查了有疼痛症状的肩袖肌腱病患者肩峰下囊的组织学特征，并通过实时聚合酶链反应、蛋白质免疫印迹和/或免疫组织化学/免疫荧光染色，研究了患病肌腱和滑囊组织中疼痛介质、促炎细胞因子、金属蛋白酶、生长因子和警报素的表达。然后，我们研究了表没食子儿茶素-3-没食子酸酯（EGCG）是否能降低人原代滑囊细胞中疼痛介质和促炎细胞因子的表达，并探讨了这些经EGCG处理的滑囊细胞在体外对肌腱细胞的旁分泌作用。在患病滑囊组织中观察到了新血管形成以及包括单核细胞/巨噬细胞和肥大细胞在内的免疫细胞浸润。与同一患者的肩袖肌腱以及无症状患者滑囊相比，有疼痛症状患者的滑囊疼痛介质和促炎细胞因子的mRNA表达更高。EGCG处理在体外显著抑制了白细胞介素1β（IL-1β）诱导的滑囊细胞中疼痛介质、促炎细胞因子和基质金属蛋白酶（MMPs）mRNA表达的升高；经EGCG处理的滑囊细胞的条件培养基显著降低了IL-1β诱导的人原代肌腱细胞中的表达。我们的研究表明，肩峰下囊可能是肩袖肌腱病中疼痛介质和促炎细胞因子的局部来源。此外，主要针对肩峰下囊进行EGCG治疗可能是缓解肩袖肌腱病相关疼痛和症状的一种潜在策略。
