Pathogenesis-Prevention of Post-Traumatic OA

描述（由申请人提供）：爱荷华大学骨关节炎专业研究中心（SCOR）将支持和协调一个由临床、生物工程、细胞和分子生物学研究经验丰富的多学科研究小组，以推进对创伤后骨关节炎发病机制的了解，并开发预防和治疗这种疾病的创新方法。关节创伤显著增加骨性关节炎的发病风险。然而，关于创伤后骨性关节炎的发病机制和预防的研究却很少。由于这些原因，我们迫切需要提高对这种常见致残疾病的了解，以及我们预防和治疗这种疾病的能力。人类踝关节为创伤后OA的研究提供了一个独特的机会，因为原发性OA的风险较低，而创伤后OA的风险相对较高。本SCOR将验证以下假设：1)超过临界水平的急性能量吸收和慢性关节面接触应力导致创伤后踝关节骨性关节炎；2)由于软骨细胞恢复或维持关节软骨的能力下降，关节创伤后骨性关节炎的风险随着年龄的增长而增加；3)减少关节面接触应力将降低创伤后骨性关节炎的风险，并为踝关节骨性关节炎提供有效的治疗。具体项目包括：1)明确急性能量吸收和慢性关节面接触应力与创伤后踝关节骨性关节炎风险关系的前瞻性临床研究；2)降低骨性关节炎踝关节关节面接触应力作用的前瞻性临床研究；3)创伤后CIA发病机制的基础科学和实验研究。4)体外基本研究年龄和机械氧化应激对软骨细胞衰老的影响以及抗氧化防御对软骨细胞衰老的影响。这些项目将大大有助于了解创伤后CIA的发病机制，并将为预防和治疗这种疾病以及其他形式CIA的新方法奠定基础。由于整合了多学科的科学方法，专注于一个明确的研究主题，该SCOR将为快速推进对创伤后OA发病机制、预防和治疗的理解创造一个国家资源。

DESCRIPTION (provided by applicant): The University of Iowa Specialized Center of Research (SCOR) in Osteoarthritis (OA) will support and coordinate a multidisciplinary group of experienced investigators in clinical, bioengineering, cell and molecular biology research to advance understanding of the pathogenesis of post-traumatic OA, and develop innovative approaches for preventing and treating this disease. Joint trauma dramatically increases the risk for development of OA. Yet, little work has been done on the pathogenesis and prevention of post-traumatic OA. For these reasons, a clear and urgent need exists to improve the understanding of this common and disabling disorder and our ability to prevent and treat it. The human ankle joint provides a unique opportunity for the study of post-traumatic OA because of the low risk of primary OA and the relatively high risk of post-traumatic OA. This SCOR will test the hypotheses that: 1) exceeding critical levels of acute energy absorption and chronic articular surface contact stress causes post-traumatic ankle OA, 2) the risk of OA following joint trauma increases with age as a result of decreased ability of chondrocytes to restore or maintain the articular cartilage, and 3) decreasing articular surface contact stress will decrease the risk of post-traumatic OA and provide effective treatment for ankle OA. The specific projects will include: 1) a prospective clinical study to define the relationships between acute energy absorption and chronic articular surface contact stress and the risk of post-traumatic ankle OA, 2) a prospective clinical study of the effects of decreasing articular surface contact stress in osteoarthritic ankles, 3) basic scientific and experimental investigations of the pathogenesis of post-traumatic CIA, and 4) basic in vitro investigations of the effects of age and mechanically induced oxidative stress on chondrocyte senescence and the effects of anti-oxidant defenses on chondrocyte senescence. These projects will contribute significantly to the understanding of the pathogenesis of post-traumatic CIA and will lay the foundation for new methods of preventing and treating this disease, as well as other forms of CIA. As a result of the integrated multi-disciplinary scientific approach focused on a well-defined research theme, this SCOR will create a national resource for rapid advancements in the understanding of the pathogenesis, prevention, and treatment of post-traumatic OA.