6-Shogaol promotes bone resorption and accelerates orthodontic tooth movement through the JNK-NFATc1 signaling axis.

INTRODUCTION: Corticotomy is widely used in clinical practice to accelerate tooth movement and shorten the duration of orthodontic treatment. It is effective, but an invasive surgery is needed to induce alveolar bone osteopenia that enable rapid tooth movement. In this study, we discovered the potential of 6-shogaol as a more patient-friendly non-invasive alternative to induce transient osteopenia and accelerate tooth movement. MATERIALS AND METHODS: The effects of 6-shogaol on the bone marrow macrophages (BMM) proliferation and osteoclast differentiation, and bone resorption were determined in vitro. Sprague-Dawley rats were distributed into three groups: CON, IPinj or Localinj and euthanized at day 28. Micro-CT, histology, immunohistological, and TUNEL analysis were performed to evaluate the tooth movement acceleration effect of 6-shogaol. RESULTS: In vitro, 6-shogaol promotes osteoclast differentiation and functional demineralization of alveolar bone. RANKL-induced mRNA expression of osteoclastic-specific genes was significantly higher in the presence of 6-shogaol. A dose-dependent increase in the area of TRAP-positive cells was observed with 6-shogaol treatment. F-actin ring formation and increased bone resorption confirmed that osteoclasts treated with 6-shogaol were mature and functional. 6-shogaol stimulated JNK activation and NFATc1 expression during osteoclast differentiation. In vivo, 6-shogaol promotes alveolar bone transient osteopenia and accelerates orthodontic tooth movement. Alveolar bone mass was reduced, more osteoclasts were observed in bone resorption lacunae on the compression side, and the expression of RANKL and sclerostin were higher than the control group. In conclusion, our results suggest that 6-shogoal accelerates tooth movement by inducing osteopenia by a mechanism similar to surgically induced bone injury.

Postnatal Development of the Spheno-occipital Synchondrosis: A Histological Analysis.

The spheno-occipital synchondrosis (SOS) in cranial base is an important growth center for the craniofacial skeleton, and also is a guide rail for development of the maxilla, midface, and mandible. Previous studies showed that SOS may be a treatment target for youngsters with midfacial hypoplasia and small cranial vault secondary to craniosynostosis. However, most of studies about the SOS are based on imaging data. In this study, we try to explore the characteristics of postnatal development of the mouse SOS based on histological analysis. Our findings showed that the width of the SOS in mice were gradually decreased from newborn mice to adult mice, and the SOS cartilage was gradually became small, then almost completely ossificated in adult mice. The resting and proliferative layers in SOS cartilage were gradually decreased, and almost only hypertrophic chondrocytes while no resting and proliferative layer chondrocytes in adult mice. The proliferative ability of SOS chondrocytes also gradually decreased. These findings will be of benefit for the further clinical treatment for patients with midfacial hypoplasia or small cranial vault secondary to craniosynostosis. Further evidence-based research about the clinical implication is necessary in future.

Effect of intermittent tensile stress on cytoskeleton of bone marrow mesenchymal stem cells during osteogenic differentiation in osteoporosis rats / 中国组织工程研究

BACKGROUND:Cytoskeleton plays an important role in the transduction of mechanical signal, and intermittent tensile stress can promote osteogenic differentiation. However, there is no relevant study about the change of cytoskeleton in osteoporosis rat bone marrow mesenchymal stem cells under intermittent tensile stress. OBJECTIVE:To investigate the effects of intermittent tensile stress on the cytoskeleton of osteoporosis rat bone marrow mesenchymal stem cells during osteogenic differentiation. METHODS:Bone marrow mesenchymal stem cells were obtained from osteoporosis rats and cultured in vitro. The 5%, 10%and 15%tensile stress were strained on the bone marrow mesenchymal stem cells through FX-4000T Flexcell. No stress was in the control group. Osteogenic differentiation of bone marrow mesenchymal stem cells was observed through alkaline phosphatase staining, while the change of cytoskeleton was observed by confocal laser scanning microscopy with figures col ected for analysis by Image-ProPlus 6.0 software. The area of cells, ratio of length to width and integrated fluorescence intensity of cytoskeleton protein F-actin were measured. RESULTS AND CONCLUSION:Under tensile stress, bone marrow mesenchymal stem cells from osteoporosis rats arranged in the direction vertical to mechanical stimulation. cells under different tensile stress differentiated towards osteoblasts. The result of alkaline phosphatase staining showed the most significant difference in 10%group, and quite an amount of cells lining lost succession in the 15%group. Under stress, the F-actin filaments were rearranged in paral el accordingly, which showed a reconstruction of cytoskeleton. Imaging analysis indicated that the area of bone marrow mesenchymal stem cells was decreased in 10%and 15%groups (P<0.05) with the increased ratio of length to width (P<0.05), and expression of F-actin increased in5%, 10%, 15%groups (P<0.05) after tensile stress. Under mechanical stimulation, the cytoskeleton of bone marrow mesenchymal stem cells from osteoporosis rats is shown to have corresponding alterations during osteogenic differentiation.