Abrine promotes cell proliferation and inhibits apoptosis of interleukin-1β-stimulated chondrocytes via PIM2/VEGF signalling in osteoarthritis

Osteoarthritis (OA), a common joint disorder with an increasing incidence worldwide, severely affects the quality of life of patients. In Chinese herbal medicine, Abrus cantoniensis Hance is considered to exert protective effects on the liver and to have beneficial effects on the gallbladder; additionally, it has antibacterial and anti-inflammatory properties, as well as the ability to enhance immunity, scavenge free radicals, regulate smooth muscle function, and improve endurance. Abrine extracted from A. cantoniensis Hance has been reported as a main functional compound capable of treating chronic inflammation.

We demonstrated that abrine promoted cell proliferation and inhibited apoptosis in IL-1β-stimulated C28/I2 cells through PIM2/VEGF signalling. These findings indicate PIM2 to be a potential drug target. Moreover, abrine has potential applicability as a therapeutic agent against OA.

The effect of abrine in vitro was analysed by Cell Counting Kit 8 assays, colony formation assays, enzyme-linked immunosorbent assay, flow cytometry analysis, quantitative real-time PCR, and western blotting using human transformed chondrocyte cell line C28/I2. The effect of abrine was evaluated in vivo using the anterior cruciate ligament transection (ACLT) Sprague-Dawley rat OA model.

In this study, we explored the effect of abrine on OA progression. Study design: Bioinformatics analysis was performed on abrine and its potential targets in OA, using the Comparative Toxicogenomics Database, GSE1919 dataset from the Gene Expression Omnibus database, Gene Set Enrichment Analysis, and docking interaction analysis.

Abrine enhanced the proliferation of interleukin (IL)-1β-stimulated C28/I2 cells in a dose-dependant manner. Expression of pro-inflammatory cytokines was induced by IL-1β treatment, whereas abrine treatment repressed the induction of C28/I2 cells in a dose dependant manner (p < 0.05). Abrine induced cell proliferation and inhibited apoptosis in IL-1β-stimulated C28/I2 cells (p < 0.05). Abrine also inhibited Proviral Integrations of Moloney virus 2 (PIM2) expression in IL-1β-stimulated C28/I2 cells (p < 0.05). The expression of vascular endothelial growth factor (VEGF), p-VEGFR2, and p-eNOS was induced by IL-1β treatment in C28/I2 cells, while abrine inhibited this induction in a dose dependant manner. Treatment with abrine decreased the expression levels of PIM2 and VEGF in IL-1β-stimulated C28/I2 cells (p < 0.05). Overexpression of PIM2 induced cell proliferation and inhibited apoptosis in IL-1β-stimulated C28/I2 cells, while VEGF silencing reversed this effect (p < 0.05). Finally, abrine prevented cartilage degradation in the ACLT model.