Low-intensity pulsed ultrasound regulates osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling for orthodontic alveolar bone remodeling

Abstract

Background: The limited regenerative potential of periodontal tissue remains a challenge in orthodontic treatment, especially with respect to alveolar bone remodeling. The dynamic balance between the bone formation of osteoblasts and the bone resorption of osteoclasts controls bone homeostasis. The osteogenic effect of low-intensity pulsed ultrasound (LIPUS) is widely accepted, so LIPUS is expected to be a promising method for alveolar bone regeneration. Osteogenesis is regulated by the acoustic mechanical effect of LIPUS, while the cellular perception, transduction mode and response regulation mechanism of LIPUS stimuli are still unclear. This study aimed to explore the effects of LIPUS on osteogenesis by osteoblast-osteoclast crosstalk and the underlying regulation mechanism.Methods: The effects of LIPUS on orthodontic tooth movement (OTM) and alveolar bone remodeling were investigated via rat model by histomorphological analysis. Mouse bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes (BMMs) were purified and used as BMSC-derived osteoblasts and BMM-derived osteoclasts, respectively. The osteoblast-osteoclast co-culture system was used to evaluate the effect of LIPUS on cell differentiation and intercellular crosstalk by Alkaline phosphatase (ALP), Alizarin Red S (ARS), tartrate-resistant acid phosphatase (TRAP) staining, real-time quantitative PCR, western blotting and immunofluorescence.Results: LIPUS was found to improve OTM and alveolar bone remodeling in vivo, promote differentiation and EphB4 expression in BMSC-derived osteoblasts in vitro, particularly when cells were directly co-cultured with BMM-derived osteoclasts. LIPUS enhanced EphrinB2/EphB4 interaction between osteoblasts and osteoclasts in alveolar bone, activated the EphB4 receptor on osteoblasts membrane, transduced LIPUS-related mechanical signals to the intracellular cytoskeleton, and gave rise to the nuclear translocation of YAP in Hippo signaling pathway, thus regulating cell migration and osteogenic differentiation.Conclusions: This study shows that LIPUS modulates bone homeostasis by osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling, which benefits the balance between OTM and alveolar bone remodeling.

Low-intensity pulsed ultrasound promotes the osteogenesis of mechanical force-treated periodontal ligament cells via Piezo1

“…The effect of LIPUS on accelerating tooth movement may be attributed to its promotion of osteoclast differentiation (Trackman et al, 2013;Feres et al, 2016;Zhou et al, 2023). In this study, LIPUS enhances osteoclastic differentiation and accelerates OTM from the third day, which is consistent with other research (Zhou et al, 2023).…”

“…Additionally, several animal experiments showed that LIPUS could accelerate tooth movement in rats ( Trackman et al, 2013 ; Alazzawi et al, 2018 ; Arai et al, 2020 ). The effect of LIPUS on accelerating tooth movement may be attributed to its promotion of osteoclast differentiation ( Trackman et al, 2013 ; Feres et al, 2016 ; Zhou et al, 2023 ). In this study, LIPUS enhances osteoclastic differentiation and accelerates OTM from the third day, which is consistent with other research ( Zhou et al, 2023 ).…”

“…The effect of LIPUS on accelerating tooth movement may be attributed to its promotion of osteoclast differentiation ( Trackman et al, 2013 ; Feres et al, 2016 ; Zhou et al, 2023 ). In this study, LIPUS enhances osteoclastic differentiation and accelerates OTM from the third day, which is consistent with other research ( Zhou et al, 2023 ). However, there is no significant difference in the number of TRAP-positive osteoclasts accumulating at the alveolar bone between the Force group and the Force + LIPUS group on day 7.…”

“…Furthermore, long-term orthodontic treatment induced alveolar bone resorption and periodontal supporting tissue destruction are caused by upregulated osteoclast activity and downregulated tissue repair capacity under pressure ( Feng et al, 2016 ; Wang et al, 2018 ; Zhou et al, 2023 ). Therefore, the balance between tissue destruction and repair during orthodontic treatment is crucial for maintaining periodontal health ( Meikle, 2005 ; Li et al, 2021 ).…”

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

“…In vivo , the rats under anesthesia were placed at a constant location, after which the transducer was pressed against the side of the cheek closest to the maxillary first molar. In vitro , we attached the transducer to the bottom of the plate corresponding to the well[ 18 ].…”