Alpha-2-Macroglobulin-Enriched Plasma Modulates Inflammatory and Proteolytic Pathways in Experimental Equine...

Joint inflammation and extracellular matrix degradation are major contributors to the development of equine osteoarthritis and reduced athletic performance. Alpha-2-macroglobulin is a naturally occurring broad-spectrum inhibitor of proteases and inflammatory mediators that has emerged as a promising orthobiologic therapy. This study investigated the anti-inflammatory and matrix-protective effects of alpha-2-macroglobulin-enriched plasma in complementary in vitro and ex vivo equine models. Primary equine chondrocytes and synoviocytes isolated from healthy horses were stimulated with interleukin-1β or lipopolysaccharide and treated with alpha-2-macroglobulin-enriched plasma or matched platelet-poor plasma. In parallel, an equine tendon explant model challenged with collagenase was used to evaluate extracellular matrix preservation. Alpha-2-macroglobulin-enriched plasma significantly reduced the production of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-13, downregulated interleukin-1β gene expression, and partially restored collagen type II expression in inflamed joint cells compared with platelet-poor plasma. In tendon explants, treatment preserved tissue architecture, reduced collagen degradation, and improved histological indices of matrix integrity under proteolytic challenge. These findings demonstrate that alpha-2-macroglobulin-enriched plasma exerts anti-inflammatory, anti-catabolic, and matrix-protective effects in experimental equine tissues. The results provide mechanistic support for the development of alpha-2-macroglobulin-based orthobiologic therapies as a complementary strategy for the management of synovitis and early osteoarthritis in horses.