Rodeo S A, Hannafin J A, Tom J, Warren R F, Wickiewicz T L
Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA.
J Orthop Res. 1997 May;15(3):427-36. doi: 10.1002/jor.1100150316.
The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhesive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients undergoing surgery for another pathology who had a normal capsule and synovium. Immunohistochemical localization with monoclonal antibodies to transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, basic fibroblast growth factor, interleukin-1 beta, tumor necrosis factor-alpha, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency of cytokine staining was correlated with the clinical diagnosis. Synovial cells, fibroblasts, T-cells, and B-cells were identified with specific antibodies, and newly synthesized matrix was examined for type-I and type-III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for type-III collagen in adhesive capsulitis tissues indicated new deposition of collagen in the capsule. There was staining for transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, interleukin-1 beta, and tumor necrosis factor-alpha in adhesive capsulitis and nonspecific synovitis tissues, compared with minimal staining in normal capsule. Staining was more frequent in synovial cells than in capsular cells. The frequency of cell and matrix staining for transforming growth factor-beta, platelet-derived growth factor, and hepatocyte growth factor was greater in adhesive capsulitis tissues than in those from patients with nonspecific synovitis. No difference in the frequency of staining between primary (idiopathic) and secondary adhesive capsulitis was found. The results of this study indicate that adhesive capsulitis involves both synovial hyperplasia and capsular fibrosis. Cytokines such as transforming growth factor-beta and platelet-derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix-bound transforming growth factor-beta may act as a persistent stimulus, resulting in capsular fibrosis. Understanding the basic pathophysiology of adhesive capsulitis is an important step in the development of clinically useful antifibrotic agents that may serve as novel treatments for patients with this conditions.
本研究的目的是验证特定细胞因子参与肩关节粘连性囊炎纤维化过程的起始和演变这一假说。经机构审查委员会批准，在肩关节镜检查期间，从19例粘连性囊炎患者、14例无纤维化或粘连性囊炎临床证据的非特异性滑膜炎患者以及7例因其他病变接受手术且关节囊和滑膜正常的患者身上采集关节囊和滑膜活检样本。使用标准免疫过氧化物酶技术，用针对转化生长因子-β及其受体、血小板衍生生长因子及其受体、碱性成纤维细胞生长因子、白细胞介素-1β、肿瘤坏死因子-α和肝细胞生长因子的单克隆抗体进行免疫组织化学定位。细胞因子染色频率与临床诊断相关。用特异性抗体鉴定滑膜细胞、成纤维细胞、T细胞和B细胞，并通过免疫组织化学染色检查新合成基质中的I型和III型胶原蛋白。存在的主要细胞类型是滑膜细胞和成纤维细胞。粘连性囊炎组织中III型胶原蛋白染色表明关节囊中胶原蛋白有新的沉积。与正常关节囊的极少染色相比，粘连性囊炎和非特异性滑膜炎组织中有转化生长因子-β及其受体、血小板衍生生长因子及其受体、白细胞介素-1β和肿瘤坏死因子-α的染色。滑膜细胞中的染色比关节囊细胞中更频繁。粘连性囊炎组织中转化生长因子-β、血小板衍生生长因子和肝细胞生长因子的细胞和基质染色频率高于非特异性滑膜炎患者的组织。原发性（特发性）和继发性粘连性囊炎之间的染色频率没有差异。本研究结果表明，粘连性囊炎涉及滑膜增生和关节囊纤维化。诸如转化生长因子-β和血小板衍生生长因子等细胞因子可能参与粘连性囊炎的炎症和纤维化过程。与基质结合的转化生长因子-β可能作为持续刺激物，导致关节囊纤维化。了解粘连性囊炎的基本病理生理学是开发临床上有用的抗纤维化药物的重要一步，这些药物可能为患有这种疾病的患者提供新的治疗方法。
