Punicalin alleviates TNF-α- and IL-1β-induced chondrocyte dysfunction and cartilage metabolism via mediating FOXO3...

Forkhead box O3 (FOXO3) transcription factor is involved in chondral homeostasis of normal, aging and osteoarthritis (OA) cartilage. At present, we aimed to investigate whether FOXO3 is a target of punicalin to prevent IL-1β- and TNF-α-induced chondrocyte dysfunction in vitro and in vivo models. Cell and mouse models of chondrocyte dysfunction were established to determine the pharmacological value of hydrolyzable tannin, punicalin, which was extracted from the pomegranate. FOXO3 protein levels in the nucleus and cytoplasm were analysed using western blot. Safranine O staining was performed to evaluate the expansion of growth plate and chondrocyte differentiation in IL-1β- and TNF-α-treated mice. In IL-1β- and TNF-α-treated chondrocytes and mice, IL-1β and TNF-α evoked phosphorylation and nucleocytoplasmic shuttling of FOXO3, as well as reduced FOXO3 expression levels in the nucleus. However, punicalin treatment repressed FOXO3 phosphorylation and cytoplasmic transfer. Punicalin treatment improved IL-1β and TNF-α-induced growth inhibition and apoptosis of chondrocyte and the abnormal expansion of growth plate and hypertrophic zone. Moreover, punicalin could maintain the normal phenotype of chondrocyte via mediating multiple gene expression. Punicalin showed a beneficial effect on IL-1β- and TNF-α-stimulated chondrocytes and cartilaginous metabolic disorders via preserving the transcriptional activity of FOXO3. PRACTICAL APPLICATIONS: Our study presents a prospective adjuvant therapeutic drug, punicalin, to prevent inflammation-related cartilage injury and chondrocyte dysfunction.