Load Induced Cartilage Degeneration in the Knee

负荷引起的膝关节软骨退化

• 批准号: 7093710
• 负责人: MARIA L. ROEMHILDT
• 金额: $ 20.06万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093710
• 关键词: articular cartilage; biomechanics; biophysics; cartilage disorder; cartilage metabolism; disease /disorder model; histology; knee; laboratory rabbit; mechanical stress; model design /development; osteoarthritis

DESCRIPTION (provided by applicant): The goal of this investigation is to develop an animal model to study the role of abnormal mechanical loads in articular cartilage degeneration, particularly that analogous to osteoarthritis (OA) of the knee. The proposed model consists of a mechanical varus loading device (VLD) that is fixed to the hind limb of a New Zealand White rabbit. The VLD applies a varus moment of known magnitude to the knee while allowing normal joint function. This causes a quantifiable increase in tibio-femoral contact load, AP, in the medial joint compartment. The advances made with this new approach are that these load alterations can be modified or removed at any time, and that iatrogenic trauma is minimized because no intra-articular surgery is needed. At this stage, this work is considered exploratory because, while there exists an apparent corollary from clinical experience that aberrant mechanical overload contributes to loss of cartilage integrity, the exact empirical nature of the requisite overload is not known. Before proceeding with animal studies that are necessary to understand interventions that will either exacerbate or retard degenerative processes, we need to be confident that a particular chronic mechanical burden reliably initiates cartilage degeneration processes which are not self-mitigating. The study will test the primary hypothesis: the level of cartilage degeneration (as quantified by histological scoring) is dependent on the magnitude and duration of varus load applied to the knee. Additional measures of cartilage material properties and cartilage metabolism (as quantified by assays of CPU, C2C, and CS-846) will be explored for their dependence on the magnitude and duration of varus load applied to the knee. Currently, there is no model available to study the onset and early progression of OA produced by chronic abnormal loading such as occurs with joint malalignment. Our work will lead to a new model that will have the capability to study the early changes that occur in the degenerative process with a direct link to humans.

描述（由申请人提供）：这项研究的目的是开发一种动物模型，以研究异常机械载荷在关节软骨变性中的作用，尤其是类似于膝盖的骨关节炎（OA）。所提出的模型由固定在新西兰白兔子的后肢上的机械变量加载装置（VLD）组成。 VLD在允许正常关节功能的同时，将VLD施加已知幅度的变化矩。这会导致内侧关节室中的胫骨 - 股接触负荷AP可量化。采用这种新方法取得的进步是，可以随时修改或去除这些负载改变，并且由于不需要关节内手术，因此，医源性创伤被最小化。在此阶段，这项工作被认为是探索性的，因为尽管存在明显的临床经验，但异常的机械超负荷有助于软骨完整性的丧失，但必要过载的确切经验性质尚不清楚。在进行了解会加剧或延迟退化过程的干预措施所必需的动物研究之前，我们需要确信，特定的慢性机械负担可靠地启动没有自我调查的软骨变性过程。该研究将检验主要假设：软骨变性的水平（通过组织学评分量化）取决于施加到膝盖上的变量载荷的幅度和持续时间。将探索软骨材料特性和软骨代谢（通过CPU，C2C和CS-846的测定法量化）的其他测量方法，以探索它们对施加在膝盖上的变量载荷的大小和持续时间的依赖性。当前，尚无模型来研究慢性异常载荷产生的OA的发作和早期进展，例如与关节差异发生。我们的工作将导致一个新的模型，该模型将有能力研究与人类直接联系的退化过程中发生的早期变化。