Objective      To determine the effect of zoledronate acid (ZOL) on the gene expression of spleen tyrosine kinase (Syk) and osteoclastogenesis in an osteoclast-osteoblast co-culture system.       Methods      Mice calvarial osteoblasts at passage 3 and RAW264.7 cells were co-cultured

and the cells were divided into 2 groups

control and ZOL treatment group (5×10

-7

mol/L

for 24 h). TRAP staining and dentin resorption lacunae examination were used to detect osteoclast formation and bone resorption. While

real-time PCR

Western blotting and immunofluorescent chemical assay were applied to measure Syk expression  at mRNA and protein levels.       Results      TRAP positive cells and dentin resorption lacunae were observed in both groups. However

there were less TRAP positive multi-nucleated osteoclasts and resorption lacunae in the ZOL treatment group than in the control (

P

0.01). ZOL treatment also resulted in a significant decrease in Syk mRNA and protein levels (P0.01). Immunofluorescent staining showed that Syk was strongly expressed in the cytoplasm of control group and formed actin-like rings around the cell

but

it was only weakly expressed in treatment group but no actin-like ring was found.       Conclusion      In the co-culture system

ZOL significantly inhibits osteoclast formation and bone resorption in our co-culture system

which might be due to its inhibition on Syk expression.