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Osteocytes express receptor activator of nuclear factor kappa-B ligand (RANKL) and regulate osteoclast formation. Orthodontic tooth movement (OTM) occurs by osteoclast resorption of alveolar bone. Osteocyte-derived RANKL is critical in bone resorption during OTM. Additionally, tumor necrosis factor-<jats:italic>\u03b1<\/jats:italic> (TNF-<jats:italic>\u03b1<\/jats:italic>) is important in osteoclastogenesis during OTM. Sclerostin has been reported to enhance RANKL expression in the MLO-Y4 osteocyte-like cell line. This study investigated the effect of TNF-<jats:italic>\u03b1<\/jats:italic> on sclerostin expression in osteocytes during OTM. <jats:italic>In vitro<\/jats:italic> analysis of primary osteocytes, which were isolated from DMP1-Topaz mice by sorting the Topaz variant of GFP-positive cells, revealed that <jats:italic>SOST<\/jats:italic> mRNA expression was increased when osteocytes were cultured with TNF-<jats:italic>\u03b1<\/jats:italic> and that <jats:italic>RANKL<\/jats:italic> mRNA expression was increased when osteocytes were cultured with sclerostin. Moreover, the number of TRAP-positive cells was increased in osteocytes and osteoclast precursors cocultured with sclerostin. <jats:italic>In vivo<\/jats:italic> analysis of mouse calvariae that had been subcutaneously injected with phosphate-buffered saline (PBS) or TNF-<jats:italic>\u03b1<\/jats:italic> revealed that the number of TRAP-positive cells and the percentage of sclerostin-positive osteocytes were higher in the TNF-<jats:italic>\u03b1<\/jats:italic> group than in the PBS group. Furthermore, the level of <jats:italic>SOST<\/jats:italic> mRNA was increased by TNF-<jats:italic>\u03b1<\/jats:italic>. As an OTM model, a Ni-Ti closed-coil spring connecting the upper incisors and upper-left first molar was placed to move the first molar to the mesial direction in wild-type (WT) mice and TNF receptor 1- and 2-deficient (TNFRsKO) mice. After 6 days of OTM, the percentage of sclerostin-positive osteocytes on the compression side of the first molar in TNFRsKO mice was lower than that in WT mice. In this study, TNF-<jats:italic>\u03b1<\/jats:italic> increased sclerostin expression in osteocytes, and sclerostin enhanced RANKL expression in osteocytes. Thus, TNF-<jats:italic>\u03b1<\/jats:italic> may play an important role in sclerostin expression in osteocytes and enhance osteoclast formation during OTM.<\/jats:p>","DOI":"10.1155\/2019\/9716758","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T09:29:02Z","timestamp":1561454942000},"page":"1-10","source":"Crossref","is-referenced-by-count":43,"title":["Effect of TNF-<i>\u03b1<\/i>-Induced Sclerostin on Osteocytes during Orthodontic Tooth Movement"],"prefix":"10.1155","volume":"2019","author":[{"given":"Fumitoshi","family":"Ohori","sequence":"first","affiliation":[{"name":"Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, 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