Mapping local strains in cartilage during injurious impact loading

描述(由申请人提供)：骨关节炎(OA)是美国残疾的主要原因，每年造成1280亿美元的损失，影响着近3000万人。骨性关节炎的发病与遗传易感性、慢性超负荷或关节创伤引起的急性损伤有关。急性损伤后骨性关节炎的发展尤为普遍，超过50%的损伤在伤后10-20年内发展为完全症状性骨性关节炎。尽管这一课题和几十年的研究很重要，但软骨在组织损伤过程中发生的局部机械事件仍然知之甚少。在这项建议中，我们利用新开发的显微镜和图像分析技术来确定组织如何管理其对关节负荷的微尺度反应。我们基于最近的结果(通过NIH Support R21AR054867)表明软骨表面下有一个能量吸收区域，并假设该区域的功能是通过局部吸收应变来保护下面的组织免受损害。我们还假设，改变这一区域的组织结构和改变其吸收能量的能力的条件也损害了其屏蔽底层的能力 伤害性负载的组织。确定该区域独特的机械特性与其在调节整个组织对机械损伤的反应中的作用之间的联系，将是我们理解关节损伤后软骨损伤开始的方法的根本转变。这些研究的结果对于更具临床相关性的对正常组织功能的理解至关重要，能够对人类疾病进行更有效的诊断和监测，并为更换或再生组织的努力提供基准和设计投入。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a leading cause of disability in the US affecting almost 30 million people at an annual cost of $128 billion. Initiation of OA is tid to genetic predisposition, chronic overload, or acute injury due to joint trauma. The development of OA after acute injury is particularly prevalent with more than 50% of injury developing full blown symptomatic OA 10-20 years after injury. Despite the importance of this topic and decades of research, the local mechanical events that occur in cartilage during tissue injury are still poorly understood. In this proposal we take advantage of newly developed microscopy and image analysis techniques to determine how the organization of the tissue governs its microscale response to joint loading. We build on recent results (through NIH support R21AR054867) showing that cartilage has an energy absorbing region just below its surface and hypothesize that the function of this region is to protect underlying tissue from damage by locally absorbing the strain. We also hypothesize that conditions that alter the organization of this region and alter its ability to absorb energy also compromise its ability to shield underlying tissue from injurious loads. Identifying the link between the unique mechanical properties of this region and its role in regulating the response of the tissue as a whole to mechanical injury would be a fundamental shift in our approach towards understanding the initiation of cartilage damage after joint injury. Results from these studies are critical to developing a more clinically relevan understanding of function in normal tissue, enabling more effective diagnosis and monitoring of human disease, and providing benchmarks and design input for efforts to replace or regenerate tissue.