A Novel Microvesicle-Based Therapeutic Strategy of Osteoarthritis
Abstract
Osteoarthritis (OA), the most common debilitating degenerative joint disease, afflicts tilde50 million people with annual healthcare costs of greater than 3 billion dollars in the US alone. This study seeks to evaluate the feasibility of an innovative microvesicles (MV)-based therapeutic strategy. The scope of the work tests two specific hypotheses: 1) Osteoclast-derived MV has pro-chondrogenic activity on chondrocytes and anti-inflammatory activity on synoviocytes; and 2) intraarticular injections of osteoclastic MV into injured joints delays OA development and may even promote articular cartilage regeneration. Aim 1 tests hypothesis 1 by establishing that osteoclastic MV has pro-chondrogenic activity on articular chondrocytes, anti-inflammatory action on inflamed synoviocytes, and osteogenic activity on osteoprogenitors, that these skeletal activities are unique to MV and not to apoptotic bodies (AB) and exosomes (Exo) of osteoclasts, and that these skeletal activities are unique to MV released by osteoclasts but not those by skeletal cells of the mesenchymal lineage, such as osteoblasts, articular chondrocytes, and synoviocytes. Aim 2 tests hypothesis 2 by comparing the relative effectiveness of a single intraarticular injection of MV with that of biweekly intraarticular injections of osteoclastic MV on prevention or delay of the progression of OA after an intraarticular tibial plateau injury, determining an optimal dose range of osteoclastic MV, and demonstrating that the treatment is effective in reversing the key pathophysiological symptoms of OA when it is initiated after OA has already been developed. The reporting year focused on work of Aim 1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2024
- Accession Number
- AD1227018
Entities
People
- Kin-hing W. Lau