TNF-α is responsible for the contribution of stromal cells to osteoclast and odontoclast formation during orthodontic tooth movement

Abstract

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.

γδT Cells Are Essential for Orthodontic Tooth Movement

“…This study demonstrates the critical role of γδT cells in OTM by affecting mechanical force-induced osteoclastogenesis. This novel mechano-immunological role of γδT cells resolves contradicting reports demonstrating that while T cells mediate OTM, depletion of CD4 + or CD8 + T cells has no impact on this process (Yan et al 2015;Ogawa et al 2019). The capability of γδT cells to sense stress signals and to be involved in tissue repair (Jameson et al 2002;Correia et al 2013) further favors the role of these cells in orthodontic treatment in which tissue damage and expression of stress molecules are inherent.…”

“…T cells were shown to be critical for such mechanical force-driven bone resorption (Yan et al 2015), likely due to their capability to regulate osteoclastogenesis by the secretion of various cytokines (Takayanagi et al 2000). Nevertheless, depletion of either CD4 + or CD8 + T cells has no 984774J DRXXX10.1177/0022034520984774Journal of Dental Research<span class="symbol" cstyle="symbol">γ</span><span class="symbol" cstyle="symbol">γ</span>T Cells Are Essential for Orthodontic Tooth Movement research-article2021 impact on OTM (Ogawa et al 2019), thus questioning the mechano-immunological role of these T-cell subsets in OTM.…”

Current Trends in In Vitro Modeling to Mimic Cellular Crosstalk in Periodontal Tissue

“…[35,36] When mechanical loading is absent, PDL cells attract osteoclast precursors via Intercellular Adhesion Molecule 1 (ICAM1) presentation and support the expression of osteoclastogenesis-beneficial molecules such as RANKL, macrophage colony-stimulating factor (MCSF), HMGB1, and tumor necrosis factor-(TNF-). [37,38] During mechanical loading and OTM, alteration of the ECM features occurs due to a release of soluble factors, that may exhibit either positive or negative effects on PDL remodeling and eventually trigger a local inflammatory response. [39][40][41][42] Periodontal ligament fibroblasts (PDLFs), PDLSCs, and cementoblasts have been investigated in in vitro and in vivo models focusing on the secretion of cytokines and growth factors turnover during remodeling and regeneration.…”

Inhibitory effect of baicalin on orthodontically induced inflammatory root resorption in rats

“… 34 In addition, TNF-α plays an important role in compressive-force-induced odontoclast formation and root resorption during orthodontic tooth movement. 35 Therefore, Runx-2 and TNF-α are suitable markers for osteoblasts and osteoclasts, respectively. 36 Immunohistochemical staining showed that the Runx-2 expression level on the tension side was significantly higher in the baicalin group than in the negative control group, while the TNF-α expression level on the pressure side was significantly lower in the baicalin group than in the negative control group.…”