Objective:To investigate the effect of lipopolysaccharide(LPS)on hypoxia-induced factor-1α(HIF-1α)expression in RAW264.7 cells under hypoxia condition and to discuss its effect on bone resorption of periodontitis associated osteoclast. Methods:RAW264.7 cells were treated with demanded concentration of LPS(1 μg/m L)under hypoxia condition. The expression of HIF-1α protein level was detected by Western blot and m RNA level was detected by q RT-PCR. Meanwhile

related signal molecules of p38/MAPK and NF- κB signaling pathways were determined. The changes of inflammatory cytokines(such as TNFα

PGE2

IL-1β)genereated by LPS-induced Raw264.7 cells and the expression of osteoclast-specific markers(such as Traf6

Nfatc1

Ctsk

c Fos

Trap) were measured by ELISA and fluorescence q RT-PCR after small inteferring RNA knocking-down HIF-1αexpression. Results:Under hypoxia condition

HIF-1α expression in cells induced by LPS for 3 h

6 h

9 h

12 h increased significantly compared with cells treated with LPS for 1 h(P=0.000

P=0.000

P=0.000

P=0.000). Under hopoxia condition

HIF-1αm RNA expressions in cells induced by LPS(0.81±0.14)were higher than those of pure hypoxia group(0.21±0.05)

with significant differences between the two groups(P=0.000). Under hypoxia condition

LPS caused up-regulation of the phosphorylation of p38/MAPK(P=0.009)

and reversely suppressed the expression of HIF- 1α by different specific inhibitors of p38/MAPK and NF-κB(P=0.011

P=0.039). After si RNA knocking down HIF-1α

LPS caused significant suppression in the level of PGE2(94.46±8.89)and IL-1β(83.96 ±7.71);there were significant differences in PGE2(134.66 ±21.11) and IL-1β(121.34 ±20.42) compared with those of si RNA-control group(P=0.008

P=0.008).Simutaneously

m RNA expressions of Traf6(0.50±0.20)and Nfatc1(0.60±0.30)were suppressed in si RNA-HIF-1α group compared with expressions of Traf6(1.00±0.00)and Nfatc1(1.00±0.00)in si RNA-control group(P=0.000

P=0.000). Conclusion:LPS can induce HIF-1α expression of RAW264.7 cells under hypoxia possibly by simultaneously activating the p38/MAPK and NF-κB signal pathway.The application of si RNA targeting HIF-1a could effectively suppress the expression of inflammatory cytokines and the osteoclast-differentiation of RAW264.7 cells induced with LPS under hypoxia condition.