# Poricoic Acid A Attenuates Osteoarthritis Progression by Stabilizing PTEN and Suppressing PI3K/AKT Signaling

## TL;DR

Poricoic acid A, a natural compound, may help treat osteoarthritis by stabilizing a protein called PTEN and reducing harmful signaling.

## Contribution

The study reveals a new therapeutic mechanism of poricoic acid A in osteoarthritis through PTEN stabilization and PI3K/AKT suppression.

## Key findings

- Poricoic acid A reduced cartilage degradation and inflammation in a mouse model of osteoarthritis.
- Poricoic acid A suppressed PI3K/AKT signaling by stabilizing PTEN protein.
- PTEN inhibition negated the protective effects of poricoic acid A in cartilage cells.

## Abstract

Osteoarthritis (OA) is characterized by chronic inflammation, and progressive cartilage degradation. Poricoic acid A (PAA), a triterpenoid compound derived from Poria 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.