PROTEOGLYCAN STRUCTURE, METABOLISM AND ROLE IN TENDON

这项研究的长期目标是更好地了解 细胞外基质的组成和材料特性 基质受到机械力的影响， 是受。 实验提出了调查的 蛋白多糖成分的结构、代谢和作用 正常致密规则结缔组织的细胞外基质， 肌腱 牛深屈肌的一个区域的转化 将肌腱变成抗压结构， 大量的大蛋白多糖和纤维软骨 组织将被记录生化和组织学， 从新生动物开始走路到 是完全发展起来的。 另外，牛屈肌腱的碎片 将保持在培养物中，并进行长期受控培养。 利用设计和制造的装置进行循环压缩加载 被调查者。 压缩载荷的能力， 维持组织中大的软骨样蛋白聚糖的合成 在体内产生这种分子的肌腱区域， 测试，使用生物化学和免疫测定。 此外，本发明还提供了一种方法， 对钢筋束压缩载荷的响应， 通常显示这种纤维软骨分化，年轻人 尚未显示出这种分化的组织将被 评估。 待检验的假设是， 肌腱通过合成特定的 分子组分，如大蛋白聚糖， 负责该基质的适当材料性质。 大小蛋白聚糖合成的调节 通过对培养物中的肌腱施加张力， 研究了 分子探针被开发用来识别 将评估软骨中的大蛋白聚糖蛋白， 与来自张应力和压缩应力的细胞中的mRNA杂交 这种特异性RNA的相对表达将 在每个肌腱区域中确定。 此外，外观 以及负责制造软骨的细胞的定位 在压缩载荷下的类似分子将使用 原位杂交技术。 恢复受损肌腱的功能是一个困难的医疗问题。 问题. 青少年肌腱与成人肌腱性能的比较研究 成纤维细胞调节蛋白多糖的合成，从而改变 其细胞外基质的功能特性是相关的 基础细胞和组织生物学以及 更合理的外科手术和治疗。

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.