PROTEOGLYCAN STRUCTURE, METABOLISM AND ROLE IN TENDON

这项研究的长期目标是更好地理解 细胞外物质的组成和性质是如何 矩阵受该矩阵所受的机械力的影响 是受制于。建议进行实验，以研究 蛋白质多聚糖组分的结构、代谢及作用 正常致密规则结缔组织的细胞外基质， 肌腱。牛深屈肌区的移位 肌腱变成了抗压结构，含有增加的 大量的蛋白多糖和一种纤维软骨 组织将被记录在生化和组织学上， 从刚出生的动物开始行走到该区域 是完全发展起来的。此外，牛屈肌腱的碎片 将长期保存在文化中并受到控制 使用设计和制造的装置的循环压缩载荷 被调查人员发现。压缩载荷作用的能力 维持组织中大的软骨样蛋白多糖的合成 在体内制造这种分子的肌腱区域将是 用生化和免疫学方法进行检测。此外, 肌腱对压缩负荷的反应 正常情况下表现为纤维软骨的分化，而年轻的 尚未表现出这种分化的组织将是 评估过了。需要检验的假设是，成纤维细胞 肌腱对压缩力的反应是通过合成特定的 分子成分，如大的蛋白多糖，是 负责该基质的适当材料特性。 大、小蛋白多糖合成的调控 通过在肌腱上施加张力力，培养也将 调查过了。为识别核心而开发的分子探针 软骨中的大蛋白多糖的蛋白质将被评估 张力性和紧张性关节细胞中的mRNA杂交 肌腱区域这种特定RNA的相对表达将 在每个肌腱区域确定。此外，外观， 以及负责产生软骨的细胞的定位- 类似的分子在压缩载荷下将被确定，使用 原位杂交技术。 恢复受损肌腱的功能是一项艰巨的医学任务 有问题。青壮年肌腱功能的调查研究 成纤维细胞调节蛋白多糖的合成，从而改变 它们的细胞外基质的功能特性是相关的 对基础细胞和组织生物学以及对 更合理的手术程序和治疗方法。

The long term objective of this research is to better understand how the composition and material properties of an extracellular matrix are influenced by the mechanical forces to which that matrix is subjected. Experiments are proposed to investigate the structure, metabolism and role of proteoglycan constituents in the extracellular matrix of a normal dense regular connective tissue, tendon. The transformation of a region of bovine deep flexor tendon into a compression-resistant structure containing increased amounts of large proteoglycans and a fibrocartilaginous organization will be documented biochemically and histologically, from the time that a newborn animal begins to walk until the region is fully developed. In addition, pieces of bovine flexor tendon will be maintained in culture and subjected to controlled long term cyclic compressive loading utilizing a device designed and built by the investigators. The ability of compressive loading to maintain synthesis of large, cartilage-like proteoglycans in tissue from regions of tendon that make such molecules in vivo will be tested, using biochemical and immunological assays. In addition, the response to compressive loading of tendon that does not normally show this fibrocartilaginous differentiation, and of young tissue that has not yet shown this differentiation, will be assessed. The hypothesis to be tested is that fibroblasts of tendon respond to compressive forces by synthesizing specific molecular components, such as large proteoglycans, that are responsible for the appropriate material properties of that matrix. The regulation of synthesis of both large and small proteoglycans by application of tensile forces to tendon in culture will also be investigated. Molecular probes developed to recognize the core protein of large proteoglycans in cartilage will be assessed for hybridization to mRNA in cells from the tensional and compressional regions of tendon The relative expression of this specific RNA will be determined in each tendon region. In addition, the appearance and localization of cells responsible for producing the cartilage- like molecules under compressive loading will be determined, using in situ hybridization techniques. Restoration of function to a damaged tendon is a difficult medical problem. Investigation of the capability of young and adult tendon fibroblasts to modulate proteoglycan synthesis and thus alter the functional properties of their extracellular matrix is relevant both to basic cell and tissue biology as well as to development of more rational surgical procedures and therapies.