Salvianolic acid A facilitates cartilage repair in knee osteoarthritis model rats by promoting WDR5 expression.

BACKGROUND

The aim of this study was to investigate the regulation of Salvianolic acid A (SAA) on the chondrogenic differentiation of bone mesenchymal stem cells (BMSCs), and its effect on cartilage repair in knee osteoarthritis (KOA) model rats and the action mechanism.

METHODS

Immunohistochemistry was performed to detect collagen type II (COL2A1), MMP13 and caspase-3 (CASP3) expression in cartilage tissues, and Safranin-O/Fast Green staining for cartilage damage. Alcian blue staining was performed to measure chondrogenic differentiation of BMSCs. Chondrocyte apoptosis was detected by using flow cytometry.

RESULTS

SAA treatment significantly attenuated cartilage damage in KOA model rats in a dose-dependent manner, and inhibited chondrocyte apoptosis induced by IL-1β in a dose-dependent manner. Moreover, SAA treatment promoted chondrogenesis-related proteins (COL2A1 and Aggrecan) expression and inhibited catabolism-related proteins (MMP13 and MMP3) expression both in the cartilage tissues from KOA model rat and in the IL-1β-treated chondrocytes. WD repeat domain 5 (WDR5) was a downstream target of SAA, and it facilitated chondrogenic differentiation of BMSCs derived from KOA model rats (KOA-BMSCs). Importantly, the inhibition of SAA treatment to the apoptosis and catabolism of chondrocyte and the promotion of SAA treatment to chondrogenic differentiation of KOA-BMSCs were rescued by silencing WDR5.

CONCLUSION

Overall, SAA treatment could facilitate cartilage repair via inhibiting the apoptosis and catabolism of chondrocyte and promoting chondrogenic differentiation of KOA-BMSCs by promoting WDR5 expression. Our data suggested that SAA may a potential drug for the treatment of KOA.