Anabolic Interventions in Engineered Cartilage and Degenerative Joint Disease

工程软骨和退行性关节疾病的合成代谢干预

• 批准号: 7964090
• 负责人: Richard Spencer
• 金额: $ 29.71万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964090
• 关键词: Aging; Animal Model; Animals; Attenuated; Benchmarking; Biochemical; Birds; Cartilage; Cattle; Cells; Chondrocytes; Degenerative polyarthritis; Disease; Engineering; Goals; Growth; Growth Factor; Growth and Development function; Human; In Vitro; Intervention; Magnetic Resonance Imaging; Maintenance; Mechanical Stimulation; Messenger RNA; Molecular; Phenotype; Physiologic pulse; Process; Production; Source; Tissues; Translating; Ultrasonography; Work; articular cartilage; human subject; in vivo; prevent; repaired

We are establishing defined molecular, biochemical, and non-invasive magnetic resonance (MR) imaging benchmarks for articular cartilage from animals and humans. Our aim is to demonstrate that engineered cartilage will support viability of and matrix production from mammalian chondrocytes using a young bovine source, establish tissue growth which will be qualitatively similar to that produced from avian cells under comparable conditions, and establish maintenance of the hyaline phenotype. We wish to apply mechanical stimulation of chondrocytes and cartilage by application of pulsed low-intensity ultrasound (PLIUS) so as to increase expression of matrix-related mRNA and corresponding matrix production, the goal being to upregulate repair processes in an animal model of osteoarthritis (OA). Ultimately we wish to establish whether these in vitro and animal model effects will translate into treatment of OA in aging humans; that is, investigate the potential of PLIUS as a disease-modifying intervention in human subjects with early OA. Additional work involves administration of exogenous growth factors to developing tissue, both by itself and in combination with PLIUS.

我们正在为动物和人类关节软骨建立明确的分子、生物化学和非侵入性磁共振（MR）成像基准。 我们的目的是证明，工程软骨将支持使用年轻的牛源的哺乳动物软骨细胞的活力和基质生产，建立组织生长，这将是定性类似于在可比条件下从禽类细胞产生的，并建立维持透明表型。 我们希望通过应用脉冲低强度超声（pulsed low-intensity ultrasound，CIMUS）对软骨细胞和软骨施加机械刺激，以增加基质相关mRNA的表达和相应的基质产生，目标是上调骨关节炎（OA）动物模型中的修复过程。 最终，我们希望确定这些体外和动物模型效应是否会转化为老年人OA的治疗;也就是说，研究超声造影作为早期OA人类受试者疾病改善干预的潜力。 额外的工作包括将外源性生长因子单独或与BMPUS联合施用到发育中的组织。