Tooth movement is a biological process of bone remodeling induced by mechanical 
force. Sclerostin secreted by osteocytes is mechanosensory and important in bone 
remodeling. However, little is known regarding the role of sclerostin in tooth 
movement. In this study, models of experimental tooth movement were established 
in rats and mice. Sclerostin expression was investigated with 
immunohistochemistry staining, and osteoclastic activity was analyzed with 
tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells 
underwent uniaxial compression and tension stress or were cultured in hypoxia 
conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 
cells were cultured with recombinant human sclerostin (rhSCL) interference and 
then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL 
and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP 
staining. During tooth movement, sclerostin was expressed differently in 
compression and tension sites. In SOST knock-out mice, there were significantly 
fewer TRAP-positive cells than in WT mice during tooth movement in compression 
sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 
osteocyte-like cells was not different under a uniaxial compression and tension 
force, whereas hypoxia conditions significantly increased sclerostin expression 
in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the 
RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 
cells in experimental osteocyte-osteoclast co-culture. These data suggest that 
sclerostin plays an important role in the bone remodeling of tooth movement.