Rees Sarah G, Davies Janet R, Tudor Debbie, Flannery Carl R, Hughes Clare E, Dent Colin M, Caterson Bruce
Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, Museum Avenue, CF10 3US, Cardiff, UK.
Matrix Biol. 2002 Nov;21(7):593-602. doi: 10.1016/s0945-053x(02)00056-2.
Cartilage superficial zone protein/proteoglycan (SZP) or proteoglycan 4 (PRG4), has been demonstrated to have the potential for several distinct biological functions including cytoprotection, lubrication and matrix binding. In the present study, we have examined both the immunolocalisation and the mRNA expression pattern of PRG4 in tissue harvested from the compressed and tensional regions of young and mature bovine tendons. Immunohistochemical analyses, utilizing monoclonal antibody 3-A-4 which recognizes a conformational-dependent epitope on native PRG4, demonstrated that PRG4 is present predominantly at the surface of fibrocartilaginous regions of tendon, with the intensity of immunoreactivity in this region increasing with age. RT-PCR analyses revealed that the expression of PRG4 mRNA can be modulated by exposure to cytokines and growth factors. In addition, analyses of human pathological tendon revealed that PRG4 may also be expressed as an alternatively spliced form lacking exons which encode part of the N-terminal matrix-binding and cell-proliferative domain; however, it remains to be determined whether such splice variants are a feature of human tendon, regardless of disease state. Taken together, these data indicate that PRG4 may play an important cytoprotective role by preventing cellular adhesion to the tendon surface as well as providing lubrication during normal tendon function, in a manner complimentary to cartilage PRG4. Structural modifications to SZP, together with a reduction in synthesis during tendon inflammation with injury and disease may account for the formation of tendon adhesions and contribute to the overall dysfunction of the tissue.
软骨表面区蛋白/蛋白聚糖（SZP）或蛋白聚糖4（PRG4）已被证明具有多种不同的生物学功能，包括细胞保护、润滑和基质结合。在本研究中，我们检测了从年轻和成熟牛肌腱的压缩区和拉伸区采集的组织中PRG4的免疫定位和mRNA表达模式。免疫组织化学分析利用识别天然PRG4上构象依赖性表位的单克隆抗体3-A-4，结果表明PRG4主要存在于肌腱纤维软骨区的表面，该区域的免疫反应强度随年龄增长而增加。逆转录聚合酶链反应（RT-PCR）分析显示，PRG4 mRNA的表达可通过暴露于细胞因子和生长因子来调节。此外，对人类病理性肌腱的分析表明，PRG4也可能以一种选择性剪接形式表达，该形式缺乏编码部分N端基质结合和细胞增殖结构域的外显子；然而，无论疾病状态如何，这种剪接变体是否是人类肌腱的一个特征仍有待确定。综上所述，这些数据表明，PRG4可能通过防止细胞粘附于肌腱表面以及在正常肌腱功能期间提供润滑发挥重要的细胞保护作用，其方式与软骨PRG4互补。SZP的结构修饰，以及在肌腱因损伤和疾病发生炎症期间合成减少，可能导致肌腱粘连的形成，并导致组织整体功能障碍。
