Orthodontic treatment is often associated with change in periodontal health. Fixed-appliance orthodontics has been shown to produce deleterious effects on the periodontium, ranging from gingivitis to bone loss. LPS is the key bacterial component inducing pro-inflammatory cytokine gene expression. In orthodontics, mechanical forces are used to induce orthodontic tooth movement, which is governed by remodelling changes in paradental tissues. The purpose of this study is to examine the effect of mechanical stress on osteogenic differentiation and HO-1 in human PDL cells, and the effect of LPS applied with mechanical stress. This study suggests that mechanical stress, such as orthodontic force, and LPS of oral microorganism play an important role in osteogenic differentiation and production of cytoprotective HO-1 during orthodontic treatment in human PDL cells.