Abstract
BackgroundTooth movement is a unique bone remodeling process induced by mechanical stimulation. Macrophages are important in mediating inflammatory processes during mechanical load-induced tooth movement. However, how macrophages are regulated under mechanical stimulation remains unclear. Mesenchymal stem cells (MSCs) can modulate macrophage polarization during bone remodeling. Hydrogen sulfide (H2S) can be produced by MSCs and have been linked to bone homeostasis. Therefore, this study aimed to investigate whether H2S contributed to periodontal ligament stem cell (PDLSC)-regulated macrophage polarization and bone remodeling under mechanical stimulation.MethodsAn experimental mechanical load-induced tooth movement animal model was established. Changes in cystathionine-β-synthase (CBS), markers of M1/M2 macrophages, tooth movement distance, and the number of osteoclasts were examined. The conditioned medium of PDLSCs with or without mechanical loading was utilized to treat THP-1 derived macrophages for 24 h to further investigate the effect of PDLSCs on macrophage polarization. Different treatments with H2S donor, CBS inhibitor, or the inhibitor of STAT1 were used to investigate the related mechanism. Markers of M1/M2 polarization and STAT1 pathway expression were evaluated in macrophages.ResultsMechanical load promoted tooth movement and increased the number of M1-like macrophages, M1-associated pro-inflammatory cytokines, and the expression of CBS on the compression side of the periodontal ligament. The injection of CBS inhibitor or H2S donor could further repress or increase the number of M1-like macrophages, tartrate-resistant acid phosphatase-positive osteoclasts and the distance of tooth movement. Mechanistically, load-induced PDLSCs enhanced H2S production, which increased the expression of M1-associated cytokines in macrophages. These effects could be blocked by the administration of CBS inhibitor. Moreover, load-induced H2S steered M1 macrophage polarization via the STAT1 signaling pathway.ConclusionsThese data suggest a novel mechanism indicating that mechanical load-stimulated PDLSCs produce H2S to polarize macrophages toward the M1 phenotype via the STAT1 signaling pathway, which contributes to bone remodeling and tooth movement process. These results provide new insights into the role of PDLSCs in regulating macrophage polarization and mediating bone remodeling under mechanical stimulation, and indicate that appropriate H2S supplementation may accelerate tooth movement.
Highlights
Tooth movement is a unique bone remodeling process induced by mechanical stimulation
He et al Stem Cell Research & Therapy (2020) 11:112 (Continued from previous page). These data suggest a novel mechanism indicating that mechanical load-stimulated Periodontal ligament stem/progenitor cells (PDLSCs) produce Hydrogen sulfide (H2S) to polarize macrophages toward the M1 phenotype via the signal transducer and activator of transcription 1 (STAT1) signaling pathway, which contributes to bone remodeling and tooth movement process. These results provide new insights into the role of PDLSCs in regulating macrophage polarization and mediating bone remodeling under mechanical stimulation, and indicate that appropriate H2S supplementation may accelerate tooth movement
Mechanical load-induced M1-like macrophage polarization to promote alveolar bone remodeling and tooth movement depends on H2S production To explore the influence of H2S on macrophage polarization under mechanical load, we blocked or enhanced the H2S level in mice by the systemic administration of CBS inhibitor HA or H2S donor GYY4137 during tooth movement (Fig. 1a)
Summary
Tooth movement is a unique bone remodeling process induced by mechanical stimulation. Macrophages are important in mediating inflammatory processes during mechanical load-induced tooth movement. This study aimed to investigate whether H2S contributed to periodontal ligament stem cell (PDLSC)-regulated macrophage polarization and bone remodeling under mechanical stimulation. During this process, aseptic inflammation develops on the compression side of periodontal ligament, which leads to bone resorption on the compression side and bone formation on the tension side [8, 13]. Macrophages, the main immune cells and the precursors of osteoclasts, play a critical role in developing inflammation and mediating bone remodeling during tooth movement [14, 15]. How mechanical signals influence macrophage polarization and contribute to bone remodeling during tooth movement remains unclear
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