Evaluating the impact of high body mass index on cartilage deformation, cartilage metabolism, and mechanical loading in individuals with anterior cruciate ligament reconstruction

项目摘要 创伤后骨关节炎（PTOA）是前交叉韧带损伤的一种常见和严重后果 损伤和重建（ACLR），因为超过一半的患者在二十年内发展疾病， 健康相关的生活质量。最近的研究表明，发展PTOA的几率是 高体重指数（BMI）的ACLR患者更高。不幸的是， 高BMI ACLR患者PTOA风险增加尚未直接评估，因此仍不清楚 明白对ACLR患者中高BMI的潜在有害影响缺乏了解 作为本研究的动机和重点。研究人员的长期目标是确定 机制驱动的治疗方法，以减少ACLR后PTOA的发生率和进展。的 这项F31研究提案的目的是评估高BMI对多种疾病的潜在有害影响。 ACLR后12至24个月的患者的软骨健康组成部分。要全面完成 这些目标是通过利用刺激-反应策略实现的，在该策略中，跑步机行走将用作体内 机械刺激以在控制软骨健康的系统组件中产生生理反应， 由结构、生物和机械过程组成。这项建议包括三个具体目标 为了：1）确定高BMI对软骨组织弹性（即变形）的负面影响，以在体内测量软骨组织弹性（即变形）。 步行机械刺激，2）确定高BMI对软骨生物标志物的负面影响 响应于体内行走机械刺激的分解，以及3）评估BMI是否可以缓和 机械负荷与目标1和2的结果之间的关联（即软骨中的反应 变形和软骨破坏的生物标志物）。本研究具有一定的创新性， 基于系统的软骨健康评估，包括多种软骨的体内评估 对于描述ACLR后高BMI的负面影响至关重要;一种方法势在必行， PTOA发展的复杂性和多因素性。这项研究意义重大，因为它将 提高我们对ACLR后导致PTOA发展的可变因素的理解，并提供关键的 未来干预策略的目标可能会减轻或预防PTOA的发生。

PROJECT SUMMARY Post-traumatic osteoarthritis (PTOA) is a common and debilitating consequence of anterior cruciate ligament injury and reconstruction (ACLR) as over half of patients develop the disease within two decades impacting their health-related quality of life. Recent research has demonstrated the odds of developing PTOA are nearly 3 times greater in ACLR patients with high body mass index (BMI). Unfortunately, the mechanisms underlying the increased PTOA risk in ACLR patients with high BMI has not been directly evaluated and thus remains poorly understood. The lack of understanding on the potential deleterious impact of high BMI in patients with ACLR serves as the motivation and focus of this proposed research. The investigator’s long-term goal is to identify mechanistic-driven treatment approaches to decrease the incidence and progression of PTOA after ACLR. The objective of this F31 research proposal aims to evaluate the potential deleterious effects of high BMI on multiple components of cartilage health in patients who are between 12 and 24 months post-ACLR. We will accomplish these objectives by leveraging a stimulus-response strategy in which treadmill walking will be used as an in vivo mechanical stimulus to produce a physiological response in system components governing cartilage health, consisting of structural, biological and mechanical processes. This proposal encompasses three specific aims to: 1) determine the negative impact of high BMI on cartilage tissue resiliency (i.e. deformation) to an in vivo walking mechanical stimulus, 2) determine the negative impact of high BMI on biological markers of cartilage breakdown in response to an in vivo walking mechanical stimulus, and 3) evaluate if BMI may moderate the associations between mechanical loading and outcomes from Aims 1 and 2 (i.e. response in cartilage deformation and biological markers of cartilage breakdown). This study is innovative, as the application of a systems-based evaluation of cartilage health, encompassing in vivo assessments of multiple cartilage components, is critical to characterize the negative effects of high BMI after ACLR; an approach imperative given the complex, multifactorial nature of PTOA development. The proposed research is significant because it will improve our understanding of modifiable factors leading to PTOA development after ACLR and provide critical targets for future intervention strategies that may mitigate or prevent onset of PTOA.