Influence of Eccentric Exercise on Muscle and Joint Health After ACL Injury

项目摘要 这个K01指导研究科学家发展奖的目的是促进林赛·莱普利博士的 由大卫戈德哈默博士和其他熟练的肌肉骨骼训练的独立研究计划 生理学家，整形外科医生，统计学家和康涅狄格大学的工程师， 必要的科学技能和职业发展，以推动她的研究线到一个新的水平。莱普利医生的 我的长期职业目标是领导一个研究团队，专注于开发基于证据的战略，以防止 创伤后骨关节炎（PTOA）的发展。K01提供的培训将为她提供 与所需的支持，成为一个生产力的独立科学家谁是能够衡量 肌肉的炎症、神经和形态学反应以及骨和软骨健康的改变， 创伤性关节损伤和随后的康复策略。此K01的中心租户将识别 能够促进前交叉韧带（ACL）术后肌肉和关节健康的康复策略 损伤迄今为止，向心运动是ACL损伤后运动处方的标准模式。然而， 系统的回顾表明，同心圆运动不能恢复肌肉力量， PTOA的发病新出现的证据表明，通过离心运动获得的机械应力 需要启动应变传感分子，促进肌肉的恢复。我们最近 证明了在ACL重建后早期将离心运动纳入康复计划， 促进股四头肌力量恢复优于向心运动。虽然有前途，古怪 临床上通常避免运动，因为离心运动与肌肉损伤有关的概念， 一直延续在文献中，和潜在的好处，偏心肌肉仍然没有定义。 此外，离心运动预防高危人群PTOA发展的能力， 从未被研究过。提供所需的循证数据，以支持将偏心 运动到康复，我们将建立一个非侵入性的，临床上可翻译的，ACL损伤的大鼠模型 并描述生物力学改变、炎症反应和PTOA进展的时间过程（目的 1）。然后，我们将使用这个模型来报告离心运动治疗肌无力的有效性（目的是 2)促进ACL损伤后的骨和软骨健康（目的3）。核心假设是， 运动将减弱神经活动的缺陷和肌肉形态的改变，从而恢复 股四头肌力量和促进关节健康更有效地比目前的标准护理同心 ACL损伤后的运动进行这种体内研究的基本原理是， 这种康复策略的好处是最终为未来临床试验的发展提供信息， 培养必要的新技能，促进Lepley博士的独立研究计划。

PROJECT SUMMARY The purpose of this K01 Mentored Research Scientist Development Award is to promote Dr. Lindsey Lepley’s independent research program by training under Dr. David Goldhamer and other skilled musculoskeletal physiologists, orthopaedic surgeons, statisticians and engineers at the University of Connecticut, to gain the necessary scientific skills and career development to advance her research line to a new level. Dr. Lepley’s long-term career goal is to lead a research team focused on developing evidence-based strategies to prevent the development of post-traumatic osteoarthritis (PTOA). The training provided by this K01 would provide her with the needed support to become a productive independent scientist who is able to measure the inflammatory, neural, and morphological responses of muscle and alterations in bone and cartilage health to traumatic joint injury and subsequent rehabilitation strategies. The central tenant of this K01 is to identify rehabilitation strategies capable of promoting muscle and joint health after anterior cruciate ligament (ACL) injury. To date, concentric exercise is the standard mode of exercise prescription after ACL injury. Yet, multiple systematic reviews have shown that concentric exercise does not restore muscle strength and does not deter the onset of PTOA. Emerging evidence suggests that mechanical stress achieved via eccentric exercise is required to initiate strain-sensing molecules that promote the recovery of muscle. We have recently demonstrated that embedding eccentric exercise into a rehabilitation program early after ACL reconstruction promotes the recovery of quadriceps strength better than concentric exercise. Though promising, eccentric exercise is often avoided clinically, as the notion that eccentric exercise is associated with muscle injury has been perpetuated in the literature, and the underlying benefits of eccentrics to muscle remain undefined. Further, the ability of eccentric exercise to prevent the development of PTOA in a high-risk population has never been studied. To provide the evidence-based data needed to support the incorporation of eccentric exercise into rehabilitation, we will establish a non-invasive, clinically-translatable, ACL injury in a rat model and describe the time course of biomechanical alterations, inflammatory response and PTOA progression (aim 1). We will then use this model to report the effectiveness of eccentric exercise to treat muscle weakness (aim 2) and promote bone and cartilage health after ACL injury (aim 3). The central hypothesis is that eccentric exercise will attenuate deficits in neural activity and alterations in muscle morphology, thereby restoring quadriceps strength and promoting joint health more effectively than the current standard of care of concentric exercise after ACL injury. The rationale for conducting this in vivo research, which establishes the physiological benefits of this rehabilitation strategy, is to ultimately inform the development of future clinical trials and generate essential new skills that will promote Dr. Lepley’s independent research program.