Intra-Articular Injection of Alpha-2-Macroglobulin Prevents Post-Traumatic Osteoarthritis
Abstract
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 alpha-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 chondroctes culture, we found A2M labeled with VivoTagTM 680 was easy detected by fluorescence microscopy, which indicated that A2M was able to enter into the cells. Western blotting and immunoprecipitation(IP) experiments further showed that A2M was able to bind toIL-1 and inhibited IL-1 and NF-B in a dose dependent manner . IL-1Beta induced the expression of NF-B, while A2M reduced the level of NF-B induced by IL-1Beta. These findings indicated that A2M inhibits inflammation via binding to and inhibiting IL-1Beta, which blocks NF-B pathway in the chondrocytes. We just performed 8 pigs surgery on August 27-31 in vivo and will collect and analysis the cartilage 15-weeks post-op (the beginning of next year). 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1117103
Entities
People
- Lei Wei
Organizations
- Rhode Island Hospital