Anabolic Interventions in Engineered Cartilage and Degenerative Joint Disease

我们正在为动物和人类的关节软骨建立明确的分子、生化和无创磁共振(MR)成像基准。 我们的目的是证明，工程化软骨将支持哺乳动物软骨细胞的生存能力和使用年轻的牛来源的基质生产，建立组织生长，将在质量上类似于在可比条件下从禽类细胞产生的组织生长，并建立维持透明的表型。 我们希望通过应用脉冲低强度超声(PLIUS)对软骨细胞和软骨进行机械刺激，以增加基质相关mRNA的表达和相应的基质产生，目的是上调骨关节炎(OA)动物模型的修复过程。最终，我们希望确定这些体外和动物模型效应是否将转化为对老年人类骨性关节炎的治疗；也就是说，调查PLIUS作为早期骨性关节炎患者的疾病修正干预的潜力。 其他工作包括给发育中的组织注射外源生长因子，既有单独的，也有与PLIUS结合的。

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.