PROTEOGLYCAN STRUCTURE, METABOLISM AND ROLE IN TENDON

蛋白多糖的结构和作用目前知之甚少。 纤维状细胞外基质。建议进行实验，以研究 正常致密细胞外基质中的蛋白多糖成分 结缔组织，肌腱，以及在数量和类型上的调节 当肌腱受到机械改变时产生的蛋白多糖 力量。牛深屈肌腱的不同区域将被使用。 近端部分仅受到纵向拉伸，并包含 主要是一种小的硫酸皮肤素蛋白多糖(分子量等于10-5)。 同样受压力作用的远端部分有一个 更高的蛋白多糖含量，其中大部分是作为更大的分子(MW 等于10-6)。肌腱培养中的外植体将用于确定 新合成化合物的合成及周转特性 蛋白多糖存在于肌腱的每一区域。将启动细胞培养 从每个地区和数量和化学特征 将测定各自合成的蛋白多糖和胶原蛋白。这些 研究将定义基质大分子在细胞内的代谢 系统。此外，蛋白多糖在决定蛋白多糖的 肌腱的结构和材料特性将由1) 肌腱成纤维细胞培养基质的超微结构研究 已知可在体外抑制纤维形成的蛋白多糖已被 添加，2)蛋白多糖与胶原结合的体外分析，以及3) 肌腱材料性质的变化与摘除 通过酶消化从组织中提取蛋白多糖。最后， 周围基质的化学和物理性质的影响 关于肌腱成纤维细胞蛋白多糖合成的研究 在悬浮液中、胶原蛋白凝胶中和无细胞条件下培养细胞， 冻干肌腱基质。蛋白多糖合成在大肠杆菌中的表达 胎儿和成人细胞将通过使培养中的细胞受到 不同的机械应力。 受损肌腱的功能恢复是一个棘手的医学问题。 肌腱成纤维细胞产生肌腱的能力研究 蛋白多糖及其大分子对基质的功能作用 因此，属性也与基础细胞生物学和组织生物学相关 在外科手术和组织再生方面的应用。

Little is known about either the structure or the role of proteoglycans in fibrous extracellular matrices. Experiments are proposed to study the proteoglycan constituents in the extracellular matrix of a normal dense connective tissue, tendon, and the modulation in both amounts and types of proteoglycan that occurs when tendon is subjected to altered mechanical forces. Distinct regions of the bovine deep flexor tendon will be used. The proximal portion is subjected to only longitudinal tension and contains predominantly a small dermatan sulfate proteoglycan (MW equal to 10-5). The distal portion which is also subject to compressional forces has a higher proteoglycan content and much of this is as a larger molecule (MW equal to 10-6). Explants of tendon in culture will be used to determine the synthetic and turnover characteristics of newly synthesized proteoglycans in each region of tendon. Cell cultures will be initiated from each region and the amounts and chemical characteristics of proteoglycans and collagen synthesized by each will be determined. These studies will define the cellular metabolism of matrix macromolecules in the system. In addition, the role of proteoglycans in determining the structural and material properties of tendon will be investigated by 1) ultrastructural study of the matrix produced by tendon fibroblast cultures to which proteoglycans known to inhibit fibrillogenesis in vitro have been added, 2) in vitro analysis of proteoglycan binding to collagen, and 3) changes in the material properties of tendon related to removal of proteoglycans from the tissue by enzymatic digestion. Finally, the influence of the chemical and physical properties of a surrounding matrix on proteoglycan synthesis by tendon fibroblasts will be determined by growing the cells in suspension, in collagen gels, and on acellular, freeze-dried tendon matrices. The expression of proteoglycan synthesis by fetal and adult cells will be modulated by subjecting cells in culture to different mechanical stresses. Restoration of fuction to a damaged tendon is a difficult medical problem. Investigation of the capabilities of tendon fibroblasts to produce proteoglycans and the functional role of these macromolecules for matrix properties is thus relevant both to basic cell and tissue biology as well as to applications in surgical procedures and tissue regeneration.