Mechanosensing by Gli1⁺ cells contributes to the orthodontic force‐induced bone remodelling

Abstract

Objectives: Gli1 + cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1 + cells respond to force and contribute to bone remodelling. Materials and methods:We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force. The transgenic mice were utilized to label and inhibit Gli1 + cells, respectively. Additionally, mice that conditional ablate Yes-associated protein (Yap) in Gli1 + cells were applied in the present study. The tooth movement and bone remodelling were analysed. Results:We first found Gli1 + cells expressed in periodontal ligament (PDL). They were proliferated and differentiated into osteoblastic cells under tensile force. Next, both pharmacological and genetic Gli1 inhibition models were utilized to confirm that inhibition of Gli1 + cells led to arrest of bone remodelling. Furthermore, immunofluorescence staining identified classical mechanotransduction factor Yap expressed in Gli1 + cells and decreased after suppression of Gli1 + cells. Additionally, conditional ablation of Yap gene in Gli1 + cells inhibited the bone remodelling as well, suggesting Gli1 + cells are force-responsive cells. Conclusions:Our findings highlighted that Gli1 + cells in PDL directly respond to orthodontic force and further mediate bone remodelling, thus providing novel functional evidence in the mechanism of bone remodelling and first uncovering the mechanical responsive property of Gli1 + cells.

Osteoclastic effects of mBMMSCs under compressive pressure during orthodontic tooth movement

“…Distances of OTM were determined under a stereomicroscope after 10 days of tooth movement according to the midpoint of the distal marginal crest of the maxillary first molar and the midpoint of the mesial marginal crest of the second molar [21]. A micro-computed tomography (Inveon, Siemens, Germany) scanner and Radi-Ant DICOM Viewer (64-bit) software were also used for analysis.…”

Mechanistic Insight into Orthodontic Tooth Movement Based on Animal Studies: A Critical Review

“…Gli1+ cells have been identified as the multipotent stem cells in adult mouse PDL [ 59 ]. Complete removal of Gli1+ cells using the inhibitors or by the genetic ablation significantly reduce OTM by 60% and diminish osteoclast formation by more than 80% [ 60 ]. On the tension side, Gli1+ increases its cell number and differentiate into osteoblasts with increased Runx2 expression during OTM [ 60 ].…”

“…Mesenchymal stem cells reside in the PDL, giving rise to PDL, alveolar bone, and cementum function as mechanosensory cells during OTM [ 60 ]. Yes-associated protein (YAP) and the paralogue transcriptional coactivator with PDZ-binding motif (TAZ), the downstream effectors of the Hippo signaling pathway, have been identified as important regulators during mechanotransduction [ 61 ].…”

“…Moreover, YAP and TAZ expression were proportional to the applied orthodontic force. A recent study investigated the role of Gli1+ cells through Yes-associated protein (YAP) activation in mouse OTM models [ 60 ].Lineage-specific deletion of the YAP in Gli1+ cells significantly reduced OTM by 50% with decreased osteoclast formation by more than 80% on compression side. On the tension side, the same transgenic mice with the YAP deletion in Gli1+ cells showed a significantly decreased proportion of Runx2+ cells by more than 80%.…”

In vivo cell proliferation analysis and cell-tracing reveal the global cellular dynamics of periodontal ligament cells under mechanical-loading

“…Recent studies suggest that specific cell populations contribute to the tissue maintenance of PDL. Hedgehog-signaling-responsive Gli1-lineage cells are present at the apical region and spread to the entire PDL in response to injury and OTM 8 , 9 . Moreover, α-smooth muscle actin 10 , Osterix/Sp7 11 , parathyroid hormone-related peptide 12 , Axin2 13 , and CD90/Thy1 14 -lineage cells also expand in the PDL space, indicating that these cells play possible roles in PDL tissue maintenance.…”