Compressive force during orthodontic tooth movement induces osteoclast formation in vivo. TNF-α plays an important role in mouse osteoclast formation and bone resorption induced by compressive force during orthodontic tooth movement. Stromal cells, macrophages and T cells take part in TNF-α-induced osteoclast formation in vitro. Root resorption caused by odontoclasts is a major clinical problem during orthodontic tooth movement. In this study, we determined the cell type targeted by TNF-α during compressive-force-induced osteoclast and odontoclast formation to elucidate the mechanism of bone and root resorption in vivo. An orthodontic tooth movement mouse model was prepared with a nickel-titanium closed coil spring inserted between the maxillary incisors and the first molar. Using TNF receptor 1- and 2-deficient (KO) mice, we found that osteoclast and odontoclast formation was mediated by TNF-α in orthodontic tooth movement. We generated four types of chimeric mice: wild-type (WT) bone marrow cells transplanted into lethally irradiated WT mice (WT>WT), KO bone marrow cells transplanted into lethally irradiated WT mice (KO>WT), WT bone marrow cells transplanted into lethally irradiated KO mice (WT>KO), and KO marrow cells transplanted into lethally irradiated KO mice (KO>KO). Using anti-CD4 and anti-CD8 antibodies, T cells were eliminated from these mice. We subjected these chimeric mice to orthodontic tooth movement. Orthodontic tooth movement was evaluated and tartrate-resistant acid phosphatase-positive cells along the alveolar bone (osteoclasts) and along the tooth root (odontoclasts) were counted after 12 days of tooth movement. The amount of orthodontic tooth movement, and the number of osteoclasts and odontoclasts on the compression side were significantly lower in WT>KO and KO>KO mice than in WT>WT and KO>WT mice. According to these results, we concluded that TNF-α-responsive stromal cells are important for osteoclast and odontoclast formation during orthodontic tooth movement.