ISOQUINOLINE ALKALOID BERBERINE ACTS AS AN INHIBITOR OF OSTEOCLAST DIFFERENTIATION

Objective: Berberine, a naturally occurring isoquinoline alkaloid, possesses a wide range of pharmacological activities, including anti-bacterial, anti-fungal, anti-protozoal, anti-inflammatory, anti-diabetes and anti-tumor properties. The purpose of this study was to investigate the effect of berberine on osteoclast differentiation of bone marrow (BM) cells obtained from BALB/c mice with zymosan-induced arthritis (ZIA). Materials and Methods: Osteoclast precursors were stimulated for 6 days under different schemes and osteoclast formation was assessed by counting the number of tartrate-resistant acid phosphatase (TRAP)-stained multinuclear cells. The expression of receptor activator of nuclear factor κB ligand (RANKL), tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TRAIL-R2 (DR5) on cultivated cells were determined by flow cytometry. Results: Berberine inhibited macrophage colony-stimulating factor (M-CSF)+RANKL-induced osteoclast differentiation and also, RANKL-independent osteoclast generation. Anti-osteoclastogenic effect of the alkaloid was related with markedly inhibited secretion of interleukin IL-1 and IL-6, with a decrease of RANKL expression on M-CSF+RANKL-stimulated BM cells, and with a lower expression of DR5. Conclusion: Our data reveal the mechanisms of blocking osteoclastic differentiation by berberine and it thus holds promise to be further investigated in vivo as a therapeutic or preventive agent for bone-related diseases such as arthritis.