We explored the effects of sclerostin removal in vivo on experimental periodontitis in mice. A ligature of Porphyromonas gingivalis-saturated collagen silk was applied to the cervical region of the first molar tooth in 10 wild-type (WT) mice and 10 sclerostin-knockout (SOST-KO) mice, and the animals were fed 10% sucrose for 2 months. Another 10 WT mice and 10 SOST-KO mice were similarly treated, but then fed a normal diet for 2 months. The maxillae were then harvested for morphological and molecular examinations. The mice with periodontitis showed significantly more severe alveolar bone loss than control mice, the most significant absorption being observed in WT mice. Immunohistochemical staining demonstrated upregulation of RANKL and ERK1/2-MAPK expression and downregulation of OPG expression in mice with periodontitis, especially WT mice. Therefore, removal of sclerostin appears to modestly protect the alveolar bone from resorption in this experimental setting. (J Oral Sci 58, 271-276, 2016).