MOLECULAR BASIS OF GROWTH FACTOR ENHANCED TENDON REPAIR

生长因子的分子基础增强肌腱修复

• 批准号: 6374827
• 负责人: Linda Ann Dahlgren
• 金额: $ 4.94万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6374827
• 关键词: SDS polyacrylamide gel electrophoresis; autoradiography; beta aminopropionitrile; binding proteins; collagen; collagenase; enzyme linked immunosorbent assay; fluorimetry; gene expression; high performance liquid chromatography; horses; immunocytochemistry; in situ hybridization; insulinlike growth factor; messenger RNA; northern blottings; nucleic acid probes; nucleic acid sequence; polymerase chain reaction; radioimmunoassay; statistics /biometry; tendon injury; transforming growth factors; ultraviolet spectrometry; wound healing

The focus of this research proposal is to define the growth factor and matrix gene expression changes in early tendon injury. It will also evaluate pharmaceutical means of enhancing the healing response to achieve tendon repair tissue that more closely resembles the mechanical properties of normal tendon. The ultimate goal is healed tendons that are less likely to sustain reinjury. Our specific aims include documentation of the temporal and spatial expression of collagen types I and III, the growth factors insulin-like growth factor I (IGF-I) and transforming growth factor beta (TGF-beta), and the IGF binding proteins during the healing response of flexor tendon following collagenase injury in the horse. The relationship between growth factor expression and subsequent changes in collagen expression are of central interest. This information will provide the scientific basis for decisions regarding selection, timing, and duration of administration of biologicals in this and future investigations. Previous in vitro studies document the beneficial effects of IGF-I on tendon healing and the in vitro study outlined in this proposal will provide preliminary data on beta-aminopriopionitrile (BAPN). The information from these in vitro studies will be combined with that from the temporal healing study to perform the two in vivo studies outlined, one using IGF-I alone and the other using a combination of IGF-I and BAPN. Tissues will be analyzed by histologic stains, in situ hybridization, immunostaining, autoradiography, and biochemical assays for DNA content and matrix composition. Statistical analyses will be performed as dictated by the specific study design, including paired t-tests, one-way analysis of variance, Tukey's post hoc comparisons, individual regression analysis, and Pearsons's Correlation. Significance will be set at p less than or equal to 0.05.

本研究提案的重点是定义早期肌腱损伤中生长因子和基质基因表达的变化。它还将评估增强愈合反应的药物方法，以实现更接近正常肌腱机械特性的肌腱修复组织。最终目标是治愈肌腱，减少再次受伤的可能性。 我们的具体目标包括记录 I 型和 III 型胶原蛋白、生长因子胰岛素样生长因子 I (IGF-I) 和转化生长因子 β (TGF-β) 以及 IGF 结合蛋白的时间和空间表达。马胶原酶损伤后屈肌腱的愈合反应。 生长因子表达与胶原蛋白表达的后续变化之间的关系是人们关注的焦点。 这些信息将为本次和未来研究中生物制剂的选择、时间安排和给药持续时间的决策提供科学依据。 先前的体外研究记录了 IGF-I 对肌腱愈合的有益影响，本提案中概述的体外研究将提供有关 β-氨基丙腈 (BAPN) 的初步数据。 这些体外研究的信息将与时间愈合研究的信息相结合，以进行概述的两项体内研究，一项单独使用 IGF-I，另一项使用 IGF-I 和 BAPN 组合。 将通过组织学染色、原位杂交、免疫染色、放射自显影以及 DNA 含量和基质组成的生化测定来分析组织。 将按照具体研究设计的规定进行统计分析，包括配对 t 检验、单向方差分析、Tukey 事后比较、个体回归分析和 Pearson 相关性。 显着性将设置为 p 小于或等于 0.05。