Qu Z, Huang X N, Ahmadi P, Andresevic J, Planck S R, Hart C E, Rosenbaum J T
Department of Medicine, Casey Eye Institute, Oregon Health Sciences University, Portland, USA.
Lab Invest. 1995 Sep;73(3):339-46.
Recent studies have implicated polypeptide growth factors in the development of rheumatoid arthritis (RA), which is characterized by synoviocyte hyperplasia and neovascularization. One such polypeptide, basic fibroblast growth factor (bFGF), is of particular interest because of its potent mitogenic and angiogenic activities. We have previously reported that cultured human synoviocytes synthesize and bind bFGF and also proliferate in response to it (1). Recently, we found a close association between increased bFGF expression and destructive changes in arthritic joints from rats (2). Now we extend our study by detecting in vivo expression of bFGF in human synovial tissues obtained from patients with RA.
Human synovial tissues from patients with RA, degenerative joint disease (DJD), and trauma were collected during joint surgery. The expression of bFGF protein and mRNA by the synovia was examined by immunolocalization, Western blot, Northern blot, and RNase protection assays. Synovium from patients with DJD and trauma was used to compare with rheumatoid synovium. Double immunostaining with cell type-specific antibodies was carried out to identify cellular sources of bFGF.
Both polypeptide and mRNA for bFGF were detected in the synovial samples examined. Increased bFGF staining was found in synovium-cartilage interface where joint destruction occurred and in hyperplastic synoviocytes of a subset of rheumatoid synovium. Strong cytoplasmic bFGF staining was localized in the majority of mast cells and vascular cells.
Synovial tissue from patients with RA, DJD, and trauma express bFGF. Increased bFGF staining in the hyperplastic lining synoviocytes and at the pannus-cartilage interface suggests that bFGF may play a role in synovial hyperplasia and joint destruction. Strong cytoplasmic bFGF staining found in mast cells and vascular cells indicates that these cells are the major sources of tissue bFGF.
近期研究表明,多肽生长因子与类风湿关节炎(RA)的发病机制有关,RA的特征是滑膜细胞增生和血管生成。其中一种多肽,即碱性成纤维细胞生长因子(bFGF),因其强大的促有丝分裂和血管生成活性而备受关注。我们之前报道过,培养的人滑膜细胞能合成并结合bFGF,且能对其产生增殖反应(1)。最近,我们发现大鼠关节炎关节中bFGF表达增加与破坏性改变之间存在密切关联(2)。现在我们通过检测从RA患者获取的人滑膜组织中bFGF的体内表达来扩展我们的研究。
在关节手术期间收集RA患者、退行性关节病(DJD)患者和创伤患者的人滑膜组织。通过免疫定位、蛋白质印迹法、Northern印迹法和核糖核酸酶保护分析检测滑膜中bFGF蛋白和mRNA的表达。使用DJD患者和创伤患者的滑膜与类风湿滑膜进行比较。用细胞类型特异性抗体进行双重免疫染色以鉴定bFGF的细胞来源。
在所检测的滑膜样本中均检测到了bFGF的多肽和mRNA。在发生关节破坏的滑膜 - 软骨界面以及一部分类风湿滑膜的增生滑膜细胞中发现bFGF染色增加。大多数肥大细胞和血管细胞中存在强烈的细胞质bFGF染色。
RA患者、DJD患者和创伤患者的滑膜组织均表达bFGF。增生的衬里滑膜细胞和血管翳 - 软骨界面处bFGF染色增加表明bFGF可能在滑膜增生和关节破坏中起作用。在肥大细胞和血管细胞中发现的强烈细胞质bFGF染色表明这些细胞是组织bFGF的主要来源。