Bone degradation is a serious complication of chronic inflammatory diseases such 
as septic arthritis, osteomyelitis, and infected orthopedic implant failure. Up 
to date, effective therapeutic treatments for bacteria-caused bone destruction 
are limited. In our previous study, we found that LPS promoted osteoclast 
differentiation and activity through activation of mitogen-activated protein 
kinases (MAPKs) pathway such as c-Jun N-terminal kinases (JNK) and extracellular 
signal regulated kinase (ERK1/2). The current study was to evaluate the 
mechanism of LPS on the apoptosis and osteoblast differentiation in MC3T3-E1 
cells. MC3T3-E1 osteoblasts were non-treated, treated with LPS. After treatment, 
the cell viability, the activity of alkaline phosphatase (ALP) and caspase-3 
were measured. The expressions of osteoblast-specific genes and Bax, Bcl-2, and 
caspase-3 were determined by real-time quantitative polymerase chain reaction 
(qPCR). Protein levels of Bax, Bcl-2, caspase-3, and phosphorylation of MAPKs 
were measured using Western blotting assays. The MAPK signaling pathway was 
blocked by pretreatment with JNK inhibitor SP600125. LPS treatment induced a 
significant decrease in cell metabolism, viability, and ALP activity in MC3T3-E1 
cells. LPS also significantly decreased mRNA expressions of osteoblast-related 
genes in MC3T3-E1 cells. On the other hand, LPS significantly upregulated mRNA 
expressions and protein levels of Bax and caspase-3 as well as activation of 
caspase-3, whereas decreased Bcl-2 expression in MC3T3-E1 cells. Furthermore, 
LPS significantly promoted MAPK pathway including the phosphorylation of JNK and 
the phosphorylation of ERK1/2; moreover, pretreatment with JNK inhibitor not 
only attenuated both of phosphorylation-JNK and ERK1/2 enhanced by LPS in 
MC3T3-E1 cells, but also reversed the downregulated expressions of 
osteoblast-specific genes including ALP and BSP induced by LPS. In conclusion, 
LPS could induce osteoblast apoptosis and inhibit osteoblast differentiation via 
activation of JNK pathway.