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方面的经验丰富的多学科研究人员组成的多学科小组，以促进对创伤后骨关节炎发病机制的理解，并开发预防和治疗这种疾病的创新方法。关节创伤极大地增加了发生骨性关节炎的风险。然而，关于创伤后骨性关节炎的发病机制和预防方面的研究还很少。出于这些原因，显然迫切需要提高对这一常见和致残障碍的认识，以及我们预防和治疗它的能力。人体踝关节原发骨性骨性关节炎风险较低，而创伤后骨性骨性关节炎风险相对较高，为创伤后骨性关节炎的研究提供了独特的机会。该SCOR将检验假设：1)超过临界水平的急性能量吸收和慢性关节表面接触应力会导致创伤性踝关节骨关节炎，2)由于软骨细胞恢复或维持关节软骨的能力降低，关节创伤后骨关节炎的风险随年龄增加而增加，3)减少关节表面接触应力将降低创伤后骨关节炎的风险，并为脚踝骨关节炎提供有效的治疗。具体项目将包括：1)确定急性能量吸收和慢性关节表面接触应力与创伤后踝关节骨关节炎风险之间的关系的前瞻性临床研究；2)降低骨性关节炎踝关节关节表面接触应力的前瞻性临床研究；3)创伤后CIA发病机制的基础科学和实验研究；4)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础体外研究。这些项目将大大有助于了解创伤后中央情报局的发病机制，并将为预防和治疗这种疾病以及其他形式的中央情报局的新方法奠定基础。作为集中于明确研究主题的多学科综合科学方法的结果，这项SCOR将创建一个在理解创伤后骨性关节炎的发病机制、预防和治疗方面快速进步的全国性资源。

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.