Piezo1 contributes to alveolar bone remodeling by activating ß-catenin under compressive stress.

INTRODUCTION: The mechanosensitive ion channel, Piezo1, is responsible for transducing mechanical stimuli into intracellular biochemical signals and has been identified within periodontal ligament cells (PDLCs). Nonetheless, the precise biologic function of Piezo1 in the regulation of alveolar bone remodeling by PDLCs during compressive forces remains unclear. Therefore, this study focused on elucidating the role of the Piezo1 channel in alveolar bone remodeling and uncovering its underlying mechanisms. METHODS: PDLCs were subjected to compressive force and Piezo1 inhibitors. Piezo1 and ß-catenin expressions were quantified by quantitative reverse transcription polymerase chain reaction and Western blot. The intracellular calcium concentration was measured using Fluo-8 AM staining. The osteogenic and osteoclastic activities were assessed using alkaline phosphatase staining, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, and Western blot. In vivo, orthodontic tooth movement was used to determine the effects of Piezo1 on alveolar bone remodeling. RESULTS: Piezo1 and activated ß-catenin expressions were upregulated under compressive force. Piezo1 inhibition reduced ß-catenin activation, osteogenic differentiation, and osteoclastic activities. ß-catenin knockdown reversed the increased osteogenic differentiation but had little impact on osteoclastic activities. In vivo, Piezo1 inhibition led to decreased tooth movement distance, accompanied by reduced ß-catenin activation and expression of osteogenic and osteoclastic markers on the compression side. CONCLUSIONS: The Piezo1 channel is a key mechanotransduction component of PDLCs that senses compressive force and activates ß-catenin to regulate alveolar bone remodeling.

Benzimidazolone-Dioxazine Pigments-Based Conjugated Polymers for Organic Field-Effect Transistor.

Molecules based on benzimidazolone-dioxazine are known as blue/violet pigments and have been commercialized for decades. However, unfavorable solubility limits the application of these structures as building blocks of conjugated polymers despite their low band gaps. Herein, a series of donor-acceptor conjugated polymers containing soluble benzimidazolone-dioxazine structures as the acceptors and oligothiophene as donors are synthesized and investigated. With increasing numbers of thiophene rings, the steric hindrance diminishes and high molecular weight polymers can be achieved, leading to an improved performance in organic field effect transistor devices. The hole mobility of polymers with three to six thiophene units is in the order of 10-1 cm2 V-1 s -1 . Among all the polymers, polymer P3 with three thiophene units between benzimidazolone-dioxazine structures shows the best hole mobility of 0.4 cm2 V-1 s -1 . Grazing-incidence wide-angle X-ray scattering results reveal that the high mobility of organic field-effect transistors (OFETs) can be accredited by matched donor-acceptor packing in the solid thin films.

The onset of adenosine monophosphate-activated protein kinase activity on orthodontic tooth movement in rats with type 2 diabetes.

Adenosine monophosphate-activated protein kinase (AMPK) plays pivotal roles in metabolic diseases including type 2 diabetes. However, the specific role of AMPK for orthodontic tooth movement in type 2 diabetes is unclear. In this study, a diabetic rat model was established through dietary manipulation and streptozocin injection. Examinations were conducted to select qualified type 2 diabetic rats. Then, an orthodontic device was applied to these rats for 0, 3, 7, or 14 days. The distance of orthodontic tooth movement and parameters of alveolar bone were analyzed by micro-computed tomography. Periodontal osteoclastic activity, inflammatory status, and AMPK activity were measured via histological analyses. Next, we repeated the establishment of diabetic rats to investigate whether change of AMPK activity was associated with orthodontic tooth movement under type 2 diabetes. The results showed that diabetic rats exhibited an exacerbated alveolar bone resorption, overactive inflammation, and decreased periodontal AMPK activity during orthodontic tooth movement. Injection of the AMPK agonist alleviated type 2 diabetes-induced periodontal inflammation and alveolar bone resorption, thus normalizing distance of orthodontic tooth movement. Our study indicates that type 2 diabetes decreases periodontal AMPK activity, leading to excessive inflammation elevating osteoclast formation and alveolar bone resorption, which could be reversed by AMPK activation.

Cyclic di-adenosine monophosphate regulates the osteogenic and adipogenic differentiation of hPDLSCs via MAPK and NF-κB signaling.

Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that can be recognized by infected host cells and activate the immunoinflammatory response. The purpose of this study is to demonstrate the effect of c-di-AMP on the differentiation of human periodontal ligament stem cells (hPDLSCs) and its underlying mechanisms. In the present study, we find that the gingival crevicular fluid (GCF) of patients with chronic periodontitis has a higher expression level of c-di-AMP than that of healthy people. In vitro, c-di-AMP influences the differentiation of hPDLSCs by upregulating Toll-like receptors (TLRs); specifically, it inhibits osteogenic differentiation by activating NF-κB and ERK/MAPK and promotes adipogenic differentiation through the NF-κB and p38/MAPK signaling pathways. Inhibitors of TLRs or activated pathways reduce the changes induced by c-di-AMP. Our results establish the potential correlation among bacterial c-di-AMP, periodontal tissue homeostasis and chronic periodontitis pathogenesis.

Effects of enamel matrix derivative on the proliferation and osteogenic differentiation of human gingival mesenchymal stem cells.

INTRODUCTION: Gingiva-derived mesenchymal stem cells (GMSCs) have recently been harvested and applied for rebuilding lost periodontal tissue. Enamel matrix derivative (EMD) has been used for periodontal regeneration and the formation of new cementum with inserting collagen fibers; however, alveolar bone formation is minimal. Recently, EMD has been shown to enhance the proliferation and mineralization of human bone marrow mesenchymal stem cells. Because the gingival flap is the major component to cover the surgical wound, the effects of EMD on the proliferation and mineralization of GMSCs were evaluated in the present study. METHODS: After single cell suspension, the GMSCs were isolated from the connective tissues of human gingiva. The colony forming unit assay of the isolated GMSCs was measured. The expression of stem cell markers was examined by flow cytometry. The cellular telomerase activity was identified by polymerase chain reaction (PCR). The osteogenic, adipogenic and neural differentiations of the GMSCs were further examined. The cell proliferation was determined by MTS assay, while the expression of mRNA and protein for mineralization (including core binding factor alpha, cbfα-1; alkaline phosphatase, ALP; and osteocalcin, OC; ameloblastin, AMBN) were analyzed by real time-PCR, enzyme activity and confocal laser scanning microscopy. RESULTS: The cell colonies could be easily identified and the colony forming rates and the telomerase activities increased after passaging. The GMSCs expressed high levels of surface markers for CD73, CD90, and CD105, but showed low expression of STRO-1. Osteogenic, adipogenic and neural differentiations were successfully induced. The proliferation of GMSCs was increased after EMD treatment. ALP mRNA was significantly augmented by treating with EMD for 3 hours, whereas AMBN mRNA was significantly increased at 6 hours after EMD treatment. The gene expression of OC was enhanced at the dose of 100 µg/ml EMD at day 3. Increased protein expression for cbfα-1 at day 3, for ALP at day 5 and 7, and for OC at week 4 after the EMD treatments were observed. CONCLUSIONS: Human GMSCs could be successfully isolated and identified. EMD treatments not only induced the proliferation of GMSCs but also enhanced their osteogenic differentiation after induction.