Pathogenesis-Prevention of Post-Traumatic OA

描述（由申请人提供）：爱荷华州大学骨关节炎（OA）专业研究中心（SCOR）将支持和协调临床、生物工程、细胞和分子生物学研究方面经验丰富的多学科研究人员，以促进对创伤后OA发病机制的理解，并开发预防和治疗这种疾病的创新方法。关节创伤显著增加了OA发展的风险。然而，很少有工作已经做了创伤后OA的发病机制和预防。由于这些原因，一个明确的和迫切的需要存在，以提高这种常见的和致残性疾病的理解和我们的能力，以预防和治疗it.The人类踝关节创伤后OA的研究提供了一个独特的机会，因为原发性OA的风险低，创伤后OA的风险相对较高。该SCOR将检验以下假设：1）超过急性能量吸收和慢性关节表面接触应力的临界水平导致创伤后踝关节OA，2）由于软骨细胞恢复或维持关节软骨的能力降低，关节创伤后OA的风险随着年龄的增长而增加，3）降低关节面接触应力将降低创伤后OA的风险，为踝关节OA提供有效的治疗。具体项目将包括：1）一项前瞻性临床研究，以确定急性能量吸收和慢性关节面接触应力与创伤后踝关节OA风险之间的关系，2）一项前瞻性临床研究，以确定降低关节面接触应力对骨关节炎踝关节的影响，3）创伤后CIA发病机制的基础科学和实验研究，和4）年龄和机械诱导的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的基本体外研究。这些项目将大大有助于了解创伤后CIA的发病机制，并为预防和治疗这种疾病以及其他形式的CIA的新方法奠定基础。由于综合多学科的科学方法集中在一个明确的研究主题，这个SCOR将创建一个国家资源，在创伤后OA的发病机制，预防和治疗的理解的快速进步。

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.