Abstract

Osteoarthritis (OA) is characterized by chronic inflammation, and progressive cartilage degradation. Poricoic acid A (PAA), a triterpenoid compound derived fromPoria cocos, exhibits anti-inflammatory and anti-fibrotic activities, but its therapeutic potential in OA remains unknown. Here, we investigated the protective effects and mechanisms of PAA in IL-1β-stimulated chondrocytes and a destabilization of a medial meniscus (DMM) mouse model. PAA significantly restored cartilage matrix synthesis, reduced inflammatory catabolism, and alleviated cartilage degeneration in vivo. RNA-seq identified PI3K/AKT signaling as a major pathway regulated by PAA. Mechanistically, PAA stabilized PTEN protein, suppressed PI3K/AKT phosphorylation, and reversed IL-1β-induced cartilage catabolism. PTEN inhibition abolished the beneficial effects of PAA. These findings identify PAA as a promising therapeutic candidate for OA and reveal PTEN-PI3K-AKT as its major regulatory axis.