A new experimental model of knee joint trauma

描述(申请人提供)：随着我们的社会试图发展更健康的生活方式，由运动、娱乐和锻炼(SRE)引起的肌肉骨骼损伤和关节疾病已经达到流行的程度。参与许多SRE活动需要保持下肢关节健康，但这种参与存在发生运动诱发或创伤性肌肉骨骼损伤的固有风险。治疗这些损伤，特别是膝关节损伤，对于保持健康的生活方式至关重要。对前十字韧带(ACL)和半月板等膝关节损伤患者的研究表明，即使在创伤性断裂后进行手术重建，也会显著增加患一种名为骨关节炎(OA)的长期慢性疾病的风险。我们推测，这一疾病过程可能是由于膝关节急性损伤期间发生的高压缩关节负荷对膝关节其他结构的隐匿性损伤所致。创伤性嵌塞期间关节接触压力高有助于解释为什么大量的损伤病例表现为骨挫伤或隐匿性骨微裂纹，以及在产生损伤的跳跃着陆后发生的覆盖软骨损伤，这通常会引发慢性病过程。令人惊讶的是，到目前为止，还没有建立动物模型来研究前交叉韧带和半月板组织断裂后创伤性损伤对膝关节的长期后果。目前的文献记载了一种骨性关节炎的关节不稳定模型，在该模型中，前交叉韧带和/或半月板受到手术损伤。然而，该模型未能解决急性事件期间关节内产生的高接触压力和组织损伤。该研究小组最近开发了一个活体动物模型，用于研究创伤性前交叉韧带和半月板损伤。为了研究创伤性关节损伤时膝关节组织的变化，为今后的临床干预研究提供初步数据，本研究将建立一种新的在体创伤性关节损伤动物模型。我们假设，在创伤后12周的退化期，与手术模型相比，创伤后12周关节软骨的退变明显更多，半月板和软骨下骨仍未被撕裂。未来骨科治疗的发展将取决于损伤后炎症、排列和疼痛问题的准确实验模型。这项拟议的研究有可能通过极大地改变用于研究膝关节骨性关节炎病理的金标准模型，来彻底改变对创伤性关节损伤的理解，从而导致创伤后骨性关节炎。这一特色模式的未来实施将鼓励转化性治疗和干预，如康复治疗或药物干预，这将推迟并有可能防止关节疼痛、残疾和最终需要进行全膝关节置换。

DESCRIPTION (provided by applicant): Musculoskeletal injuries and joint disorders due to sports, recreation and exercise (SRE) have reached epidemic proportions as our society attempts to develop a healthier lifestyle. Participation in many SRE activities requires maintenance of lower- extremity joint health, yet such involvement presents an inherent risk of developing exercise-induced or traumatic musculoskeletal injuries. Treatment of these injuries, particularly to the knee joint, is paramount in the retention of a healthy lifestyle. Studies of patients suffering knee injuries, such as to the anterior cruciate ligament (ACL) and meniscus, show that even with surgical reconstruction after traumatic rupture there is a significant increase in the risk of a long term, chronic disease called osteoarthritis (OA). We hypothesize that this disease process may be precipitated by occult damage to the other structures of the knee as a result of the high compressive joint loads that occur during the acute injury to the knee. High joint contact pressures during traumatic impaction help explain the large number of injury cases that exhibit bone bruises, or occult bone microcracks, and injury to overlying cartilage that occurs following injury- producing jump landings that often initiate the chronic disease process. Surprisingly, to date, there is no established animal model to study the long-term consequences of traumatic injury to the knee following rupture of the ACL and meniscal tissue. The current literature documents a joint instability model of osteoarthritis in which the ACL and/or meniscus is surgically damaged. However, this model fails to address the high contact pressures and tissue injuries generated in the joint during the acute event. This research team has recently developed a live animal model for the study of traumatic ACL and meniscus injury. In order to study the changes occurring in the tissues of the knee during traumatic injury and establish preliminary data for future clinical intervention studies, the current study will establish and characterize a new, in vivo animal model of traumatic joint injury. We hypothesize that there will be significantly more degeneration of the articular cartilage, remaining untorn menisci and subchondral bone during the degenerative phase of the traumatic versus the surgical model to 12 weeks post-trauma. The development of future orthopaedic treatments will hinge on accurate experimental models of post-injury inflammation, alignment, and pain issues. The proposed research has the potential to revolutionize the understanding of traumatic joint injury that leads to a post-traumatic OA by greatly altering the gold standard model used to study the pathology of knee OA. Future implementation of this characterized model will encourage translational treatments and interventions, such as rehabilitation therapies or pharmaceutical interventions, which will delay and potentially prevent joint pain, disability, and the eventual need for total knee arthroplasty.