Abstract
Osteocytes are abundant cells in bone, which contribute to bone maintenance. 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-α (TNF-α) 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-α on sclerostin expression in osteocytes during OTM. In vitro analysis of primary osteocytes, which were isolated from DMP1-Topaz mice by sorting the Topaz variant of GFP-positive cells, revealed that SOST mRNA expression was increased when osteocytes were cultured with TNF-α and that RANKL 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. In vivo analysis of mouse calvariae that had been subcutaneously injected with phosphate-buffered saline (PBS) or TNF-α revealed that the number of TRAP-positive cells and the percentage of sclerostin-positive osteocytes were higher in the TNF-α group than in the PBS group. Furthermore, the level of SOST mRNA was increased by TNF-α. 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-α increased sclerostin expression in osteocytes, and sclerostin enhanced RANKL expression in osteocytes. Thus, TNF-α may play an important role in sclerostin expression in osteocytes and enhance osteoclast formation during OTM.
Highlights
Osteocytes, derived from osteoblasts, comprise 90%–95% of cells within bone tissue; they are stellate shaped and construct an intercellular network [1]
Compared with control osteocytes, SOST mRNA expression increased in 1-day culture of Tumor necrosis factor-α (TNF-α)-treated osteocytes; there was no significant difference in 3-day culture (Figure 2(a))
Compared with osteocytes treated with 0 ng/mL recombinant human sclerostin (rhSCL), receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA expression was significantly increased in osteocytes treated with 100 ng/mL rhSCL; in contrast, OPG mRNA expression showed no significant difference on the basis of rhSCL treatment (Figures 2(b) and 2(c))
Summary
Osteocytes, derived from osteoblasts, comprise 90%–95% of cells within bone tissue; they are stellate shaped and construct an intercellular network [1]. Multiple studies have shown that osteocytes play a central role as mechanosensory cells within bone [2, 3]; notably, osteocytes regulate bone remodeling by sensing mechanical stimulation and expression of various genes and proteins [4, 5]. TNF-α has been shown to play an important role in osteoclastogenesis during orthodontic tooth movement (OTM) [13,14,15]. Sclerostin has been reported to increase RANKL expression in the MLO-Y4 osteocyte-like cell line, thereby promoting osteoclast formation [26]. Some studies have shown that sclerostin expression can be increased by mechanical stimulation in mouse models of OTM [30,31,32]. We investigated the influence of TNF-α on the expression of sclerostin in primary osteocytes, examined how TNF-α affects the expression of sclerostin in osteocytes during OTM
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