Gene Transfer Treatment of Articular Cartilage Damage

关节软骨损伤的基因转移治疗

• 批准号: 7103416
• 负责人: STEPHEN B. TRIPPEL
• 金额: $ 28.63万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-09 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103416
• 关键词: Acute; Biochemical; Biomechanics; Bos taurus; Cartilage; Cattle; Chondrocytes; Coupled; Development; Fibroblast Growth Factor 2; Future; Gene Transfer; Growth Factor; Growth Factor Receptors; Human; In Vitro; Insulin-Like Growth Factor I; Insulin-Like-Growth Factor I Receptor; Mediating; Methods; Orthopedics; Osteoarthrosis Deformans; Production; Purpose; Recombinant adeno-associated virus (rAAV); Regulation; Role; Testing; Trauma; adeno-associated viral vector; articular cartilage; autocrine; base; insight; paracrine; repaired

DESCRIPTION (provided by applicant): Articular cartilage damage remains an unsolved problem in orthopaedics. The purpose of the proposed studies is to elucidate the potential role of autocrine/paracrine mechanisms in growth factor-mediated articular cartilage repair. The studies will employ in vitro recombinant adeno-associated virus (rAAV) mediated gene transfer methods to test the following hypotheses: (1) local growth factor production can be achieved by rAAV vector-mediated gene transfer to bovine articular chondrocytes and will augment cartilage repair in acute cartilage trauma; (2) local growth factor production can be achieved by rAAV vector-mediated gene transfer of human articular chondrocytes and will augment repair of osteoarthritic cartilage; (3) local production of more than one growth factor can be achieved by rAAV vector-mediated gene transfer and expressed growth factors will interact in the regulation of repair in traumatic and osteoarthritic cartilage damage; and (4) local growth factor production, coupled with expression of growth factor receptors can be achieved by rAAV-mediated gene transfer to chondrocytes and will augment repair in traumatic and OA cartilage damage. These hypotheses will be tested using insulin-like growth factor I (IGF-I) and fibroblast growth factor-2, (FGF-2) and, in Aim 4, the type I IGF receptor (IGF-IR). Repair will be assessed using biosynthetic, histological, biochemical and biomechanical parameters. The demonstration by these studies that growth factor-mediated cartilage repair can be achieved through autocrine/paracrine mechanisms would not only lend insight into the role of these factors in cartilage regulation, but may serve to facilitate the development of future potential gene transfer-based therapies.

描述（由申请人提供）：关节软骨损伤仍然是一个问题 骨科尚未解决的问题。拟议研究的目的是 阐明自分泌/旁分泌机制在生长中的潜在作用 因子介导的关节软骨修复。该研究将采用体外 重组腺相关病毒（rAAV）介导的基因转移方法 检验以下假设：（1）局部生长因子的产生可以 通过rAAV载体介导的基因转移至牛关节软骨细胞来实现 并将增强急性软骨损伤的软骨修复； (2) 本地增长 因子生产可以通过 rAAV 载体介导的基因转移来实现 人类关节软骨细胞，将增强骨关节炎的修复 软骨； (3)可以实现一种以上生长因子的本地化生产 通过rAAV载体介导的基因转移和表达的生长因子将 在创伤性和骨关节炎软骨的修复调节中相互作用 损害; (4)局部生长因子的产生，以及表达 生长因子受体可以通过rAAV介导的基因转移来实现 软骨细胞，将增强创伤性和骨关节炎软骨损伤的修复。 这些假设将使用胰岛素样生长因子 I (IGF-I) 和 成纤维细胞生长因子-2 (FGF-2) 以及目标 4 中的 I 型 IGF 受体 (IGF-IR)。将使用生物合成、组织学、生物化学来评估修复 和生物力学参数。这些研究表明增长 因子介导的软骨修复可以通过自分泌/旁分泌来实现 机制不仅有助于深入了解这些因素在 软骨调节，但可能有助于促进未来的发展 潜在的基于基因转移的疗法。