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 year 3, we published a peer review paper entitled "A2M Inhibits Chondrocyte Catabolism by Blocking IL-1beta/NF-kappaB Pathway" on JOR. We have performed 48 pigs surgery with A2M treatment in vivo and have collected all knee joint samples. Currently, we have collected 384 slides from 48 pigs and are analyzing these samples. We are preparing the second paper entitled A Novel Mechanically Stable PTOA Model of Inflammation: Swine Pilot Study of Drilling Adjacent ACL Attachment. We plan to finish the analysis of the data we already collected and write a final report before 8/14/2023. 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.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2022
Accession Number
AD1190663

Entities

People

  • Lei Wei

Organizations

  • Rhode Island Hospital

Tags

DTIC Thesaurus Topics

  • Arthritis
  • Biological Factors
  • Biomedical Research
  • Blood
  • Cartilage
  • Catabolism
  • Cells
  • Cellular Structures
  • Chemistry
  • Connective Tissue Cells
  • Cytokines
  • Diseases
  • Gene Expression
  • Growth Factors
  • Health Services
  • Joint Diseases
  • Jointsanatomy
  • Ligaments
  • Membranes
  • Orthopedics
  • Peptide Growth Factors
  • Peptides
  • Proteins
  • Surgery

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Trauma Surgery or Emergency Medicine.