Tanshinone IIA alleviates IL-1β-induced chondrocyte apoptosis and inflammation by regulating FBXO11 expression

Highlights

• TAN IIA inhibits IL-1β from inducing apoptosis and inflammation in CHON-001 cells.

• FBXO11 overexpression inhibits the protective effect of TAN IIA on apoptosis and inflammation of CHON-001 cells.

• Suppressing PI3K/AKT and NF-κB pathways protects against apoptosis and inflammation of CHON-001 cells.

• TAN IIA treatment improves apoptosis and inflammation of chondrocytes in OA rats.

Abstract

Objective

This study explored the pharmacological mechanism of Tanshinone IIA (TAN IIA) in the treatment of Osteoarthritis (OA), which provided a certain reference for further research and clinical application of Tan IIA in OA.

Methods

CHON-001 cells were stimulated with 10 μg/mL IL-1β for 48 h and treated with 10 μM TAN IIA for 48 h. Cellular viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, and Cleaved caspase-3 was measured by Immunoblot assay and RT-qPCR. TNF-α, IL-6, and iNOS in CHON-001 cells were determined by RT-qPCR and ELISA. To further verify the effect of TAN IIA on OA, a rat model of OA in vivo was established by right anterior cruciate ligament transection. TAN IIA was administered at 50 mg/kg or 150 mg/kg for 7 weeks. The degree of cartilage destruction in OA rats was observed by TUNEL and HE staining. Cleaved caspase-3 and FBXO11 were measured by immunohistochemical staining, RT-qPCR, and Immunoblot. TNF-α, IL-6, and iNOS in chondrocytes of OA rats were detected by ELISA.

Results

IL-1β stimulated CHON-001 cell apoptosis and inflammation, and TAN IIA had anti-apoptosis and anti-inflammatory effects on IL-1β-regulated CHON-001 cells. TAN IIA down-regulated FBXO11 and inhibited PI3K/AKT and NF-κB pathways, thereby alleviating apoptotic and inflammatory reactions in CHON-001 cells under IL-1β treatment. Moreover, TAN IIA treatment improved chondrocyte apoptosis and inflammations in OA rats.

Conclusion

TAN IIA inhibits PI3K/Akt and NF-κB pathways by down-regulating FBXO11 expression, alleviates chondrocyte apoptosis and inflammation, and delays the progression of OA.

Keywords
Chondrocytes; Il-1β; Tanshinone iia; Fbxo11; PI3K/AKT; NF-κB