Inflammatory Phenotyping after Meniscus Injury to Identify those at Increased Risk of Rapid Posttraumatic Osteoarthritis Progression and Drugs that can be Repurposed

Abstract Arthroscopic meniscal procedures are the most commonly performed orthopaedic procedure in the U.S. affecting 15% of Americans ages 10-65 years. Meniscus injury is known to increase the risk of posttraumatic osteoarthritis (PTOA); however, surgical treatment alone does not eliminate PTOA risk. The overarching goals of this project are to determine whether a subset of patients with a dysregulated inflammatory response is at increased risk of symptom and structural PTOA progression, and to identify potential FDA-approved drugs that can be repurposed to alter PTOA progression after meniscus injury. The rationale supporting this approach is founded on our previous work showing that injury pathologically alters meniscus biology and promotes PTOA development. An inflammatory phenotype has been identified for those with aging-related primary OA, and we have identified a subset of patients that demonstrate a dysregulated inflammatory response after knee injury. This patient subset termed the “Inflamma-type” has been observed across multiple injury patterns that often result in PTOA including meniscus injury, knee ligament injury, and lower extremity fractures. Inflamma-type patients represent approximately 25% of these patient populations and demonstrate a lower ratio of anti-inflammatory to pro-inflammatory cytokines and increased biomarkers of cartilage degradation. By assessing synovial fluid inflammatory networks in conjunction with MRI changes, we seek to determine if the Inflamma-type experiences a more rapid progression of PTOA symptoms and/or structural changes. Additionally, we also propose a novel approach to identify FDA-approved drugs that could be repurposed to potentially alter PTOA progression.