Intra-Articular Injection of Alpha-2-Macroglobulin Prevents Post-Traumatic Osteoarthritis

Since it is known that cartilage catabolic enzymes in synovial fluid (SF) play a critical role in the onset and progression of post traumatic osteoarthritis (PTOA), the objective of this study is to demonstrate that intra-articular injection of -2 Macroglobulin (A2M), a master inhibitor of these enzymes, would serve as an early therapeutic agent to prevent PTOA after joint injury. In this proposed study, we will test whether early supplemental intra-articular A2M injections will attenuate PTOA pathogenesis 15 weeks after joint injury in the mini-pig model in vivo and we will explore the mechanism how A2M prevents PTOA via blockage IL-1/NF-kb pathway in vitro. In year 3, we published a peer review paper entitled A2M Inhibits Chondrocyte Catabolism by Blocking IL-1/NF-B Pathway on JOR. In year 4, we have collected all slides from 48 pigs and analyzed these samples. Our second paper entitled A Novel Large Animal Model of Posttraumatic Osteoarthritis Induced by Inflammation with Mechanical Stability just published on AJTR. Our third paper was published on Biomolecules entitled The Effects of an Osteoarthritic Joint Environment on ACL Damage and Degeneration: A Yucatan Miniature Pig Model. The fourth paper just submitted to AJSM entitled 2-Macroglobulin Attenuates Posttraumatic Osteoarthritis Cartilage Damage by Inhibiting Inflammatory Pathways in a Preclinical Yucatan Minipig Model. Successful implementation of an injectable therapeutic to prevent the PTOA has the potential to significantly improve the quality of life for thousands of wounded warriors, as well as maximizing their function for return to duty or civilian life. We have achieved the goals we proposed in the study successfully.