A novel peptide primes mesenchymal stem cell-derived extracellular vesicles to suppress osteoarthritis by promoting SOX9 and Collagen Type II expression 2247

Abstract Description Osteoarthritis (OA) is a chronic, irreversible joint disease marked by cartilage breakdown, osteophyte formation, and synovitis. Despite its prevalence, effective and safe disease-modifying OA drugs (DMOADs) are still lacking. This study introduces a specific peptide that primes extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) to promote chondrogenesis and treat OA. Using tangential flow filtration (TFF), we isolated peptide-primed MSC-EVs following guidelines from the International Society for Extracellular Vesicles. Therapeutic effects were evaluated in an anterior cruciate ligament transection (ACLT)-induced OA model through cartilage repair, MSC chondrogenesis stimulation, and biodistribution analysis. The peptide activates adipose-derived stem cell EVs (ADSC-EVs) via receptor X signaling, increasing chondrogenic markers like Collagen type II, COMP, and SOX9. Peptide injections alone reduced OA severity in ACLT rats, while peptide-primed MSC-EVs promoted thicker cartilage growth than controls. Mechanistically, these EVs restore Collagen type II, COMP, and SOX9, inhibit MMP13, and enhance extracellular matrix (ECM) synthesis while reducing ECM degradation. AlphaFold2-Multimer analysis identified key chondrogenic protein sequences, supporting Protein-P-MSC-EVs as a promising DMOAD strategy for OA. Funding Sources This research was funded by the Ministry of Science and Technology (MOST 111-2314-B-418-004, MOST 111-2321-B-418-002-, MOST 111-2314-B-418-003-, NSTC 112-2321-B-418-004- and NSTC 112-2314-B-418-010-MY3). Topic Categories Cytokines and Chemokines and Their Receptors (CCR)