Preventing Cartilage Degeneration after Traumatic Injury

简单地说，骨性关节炎可以理解为关节软骨的磨损， 自我修复能力有限的组织。最近的研究结果表明， 损伤后软骨的进行性降解与软骨的升高和活化密切相关 一种特殊的酶，称为金属蛋白酶。除了可能的治疗外，关节负荷 例如在物理治疗或锻炼期间会影响基质的生物合成和降解物 根据装载过程而定的事件。对机械生物学有了更好的理解 软骨损伤及循环负荷对组织降解的影响是软骨修复的重要步骤 优化软骨退行性变的治疗方法。 在这个应用中，我们假设循环负荷调节以下组织退变 损伤并影响金属蛋白酶抑制剂的疗效。利用体外培养技术 模型系统是我们实验室最近开发的，我们建议研究如何每天的负荷 (固定与低和中等循环压缩)会影响特定的降解事件 明确的骨折下损伤后软骨的处理。我们的具体目标是：1) 确定每日负荷对基质生物合成、细胞因子水平、基质降解、细胞 细胞凋亡和生物力学特性；以及2)确定基质的疗效 金属蛋白酶抑制剂(MMPI)在预防基质退变中的作用 装填。结果将在分子、细胞和结构水平上进行测试，通过确定 细胞因子水平、金属蛋白酶的升高/激活、基质(蛋白多糖和 胶原)丢失和降解，基质生物合成，胶原网络完整性(组织肿胀)， 并在损伤后7天内保持软骨的组织生物力学特性。它的意义 是两个方面，一是确定损伤软骨的力学生物学，二是了解 机械负荷如何影响治疗，如MMPI的使用。我们相信 这项研究的结果将显著影响治疗软骨退行性变的方法 创伤性骨关节炎和其他类型的关节炎。

In simplest terms, osteoarthritis can be understood as the wearing away of articular cartilage, a tissue with a limited ability to repair itself. Findings from recent studies suggest that progressive degradation in cartilage after injury is closely related to the elevation and activation of specific enzymes, called metalloproteinases. In addition to possible treatments, joint load such as during physical therapy or exercise can affect matrix biosynthesis and the degradative events depending on the courses of loading. A better understanding of the mechanobiology of injured cartilage and the effects of cyclic loads on tissue degradation is an important step for optimizing the treatments for cartilage degeneration. In this application, we hypothesize that cyclic load modulates tissue degeneration following injury and affects the efficacy of metalloproteinase inhibitors. Taking advantage of an in vitro model system developed recently in our laboratory, we propose to study how daily load (immobilization vs. low and moderate cyclic compression) affects specific degradative events and the treatments of cartilage following defined subfracture injury. Our specific aims are: 1) to determine the effects of daily load on matrix biosynthesis, cytokine level, matrix degradation, cell apoptosis, and biomechanical properties; and 2) to determine the efficacy of matrix metalloproteinase inhibitors (MMPI) on preventing matrix degeneration in the presence of daily load. The outcomes will be tested at the molecular, cellular and structural levels by determining the level of cytokines, elevation/activation of metalloproteinases, matrix (proteoglycan and collagen) loss and degradation, matrix biosynthesis, collagen network integrity (tissue swelling), and tissue biomechanical properties in the cartilage for up to 7 days after injury. The significance is two fold, first to determine the mechanobiology of injured cartilage and second to understand how mechanical load influences therapeutic treatments such as the use of MMPIs. We believe the results of this study will significantly impact the ways to treat cartilage degeneration in traumatic osteoarthritis and other types of arthritis.