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The aim of this study was to investigate the mechanism by which periodontal ligament stem cells (PDLSCs) modulate root resorption of human deciduous teeth under mechanical stress. In this investigation, the PDLSCs were derived from deciduous and permanent teeth at different stages of root resorption. A cyclic hydraulic pressure was applied on the PDLSCs to mimic chewing forces in the oral environment. The cultured cells were characterized using osteogenic and adipogenic differentiation assays, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting analysis. The PDLSCs exhibited the ability to induce osteoclast differentiation under certain mechanical stresses. As the expressions of RUNX2, alkaline phosphatase (ALP), and osteoprotegerin (OPG) were significantly reduced, the receptor activator of the nuclear factor kappa-B ligand (RANKL) was upregulated increasing the RANKL/OPG ratio. Under hydrodynamic pressure at 0-135 kPa, the expressions of alpha 7 nicotinic acetylcholine receptors (α7 nAChR), p-GSK-3β, and active-β-catenin were markedly upregulated in PDLSCs from unresorbed deciduous teeth. Treatment with the α7 nAChR inhibitor alpha-bungarotoxin (α-BTX) and the Wnt pathway inhibitor DKK1 may reverse the mechanical stress inducing upregulation of RANKL and reduction of RUNX2, ALP, and OPG. Alizarin red staining confirmed these results. The mechanical stress applied on the deciduous tooth PDLSCs can induce osteoclastic effects through upregulation of α7 nAChR and activation of the canonical Wnt pathway. It can be suggested that chewing forces may play a major role at the beginning of the physiological root resorption of deciduous teeth.

Degeneration and destruction of articular cartilage are the key characteristics of osteoarthritis (OA). In recent studies, the use of astilbin (AST), the primary active ingredient of Astilbe chinensis, has been shown to correlate with a reduction in inflammatory disease symptoms. The present study aimed to investigate the effects and mechanisms of AST on OA. A rat model of OA was constructed and in vivo experiments were performed using the AST, PBS, OA and control groups. The cartilage tissues of each group were assessed by hematoxylin and eosin and toluidine blue staining. The gene expression levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, AKT, PI3K and other related proteins were analyzed by reverse transcription-quantitative PCR and western blot analysis. AST was found to significantly inhibit IL-1β and TNF-α protein expression; this further confirmed that IL-1β, TNF-α and PI3K mRNA expression was downregulated, indicating that the protective mechanism of AST is associated with the PI3K/AKT pathway. Overall, the results of the present study demonstrate that AST can improve OA symptoms by downregulating the PI3K/AKT signaling pathway, and may therefore be a potential therapeutic option for patients with OA.

Periodontitis is the leading cause of adult tooth loss, and those who smoke are at an increased risk of developing periodontitis. α7 nicotinic acetylcholine receptor (α7 nAChR) is proposed to mediate the potential synergistic effect of nicotine and inflammation in smoking‐related periodontitis. However, this has not been experimentally demonstrated. We isolated and cultured human periodontal ligament stem cells (PDLSCs) from healthy and inflamed tissues. PDLSCs were treated with either inflammatory factors or nicotine. We measured expression of genes that are associated with osteogenic differentiation and osteoclast formation using RT‐qPCR and Western blot analyses. Besides, immunohistochemical staining, micro‐CT analysis and tartaric acid phosphatase staining were used to measure α7 nAChR expression and function. Inflammation up‐regulated α7 nAChR expression in both periodontal ligament tissues and PDLSCs. The up‐regulated α7 nAChR contributed to the synergistic effect of nicotine and inflammation, leading to a decreased capability of osteogenic differentiation and increased capability of osteoclast formation‐induction of PDLSCs. Moreover, the inflammation‐induced up‐regulation of α7 nAChR was partially dependent on the level of phosphorylated GSK‐3β. This study provides experimental evidence for the pathological development of smoking‐related periodontitis and sheds new light on developing inflammation and α7 nAChR‐targeted therapeutics to treat and prevent the disease.

Purpose To screen the novel biomarkers for gastric cancer and to determine the values of glutaminase 1 (GLS1) and gamma-glutamylcyclotransferase (GGCT) for detecting gastric cancer. Experimental design A discovery group of four paired gastric cancer tissue samples are labeled with Isobaric tag for relative and absolute quantitation agents and identified with LC-ESI-MS/MS. A validation group of 168 gastric cancer samples and 30 healthy controls are used to validate the expression of GLS1 and GGCT. Results Four hundred and thirty-one proteins are found differentially expressed in gastric cancer tissues. Of these proteins, GLS1 and GGCT are found overexpressed in gastric cancer patients, with sensitivity of 75.6% (95% CI: 69-82.2%) and specificity of 81% (95% CI: 75-87%) for GLS1, and with sensitivity of 63.1% (95% CI: 55.7-71.5%) and specificity of 60.7% (95% CI: 53.3-68.2%) for GGCT. The co-expression of GLS1 and GGCT in gastric cancer tissues has sensitivity of 78.1% (95% CI: 70.1-86.1%) and specificity of 86.5% (95% CI: 79.5-93.4%). Moreover, both GLS1 and GGCT present higher expression of 82.6% (95% CI: 68.5-99.4%) and 73.9% (95% CI: 54.5-93.3%) in lymph node metastasis specimen than those in non-lymph node metastasis specimen. The areas under ROC curves are up to 0.734 for the co-expression of GLS1 and GGCT in gastric cancer. The co-expression of GLS1 and GGCT is strongly associated with histological grade, lymph node metastasis, and TNM stage Ⅲ/Ⅳ. Conclusions and clinical relevance The present study provides the quantitative proteomic analysis of gastric cancer tissues to identify prognostic biomarkers of gastric cancer. The co-expression level of GLS1 and GGCT is of great clinical value to serve as diagnostic and therapeutic biomarkers for early gastric cancer.

The physiological root resorption of deciduous teeth is a normal phenomenon, but the mechanisms underlying this process are still unclear. In this study, deciduous dental pulp stem cells (DDPSCs) and permanent dental pulp stem cells (DPSCs) were derived from deciduous teeth and normal permanent teeth at different stages of resorption. In the middle stage of root resorption, DDPSCs exhibited an increase in the ability to induce osteoclast differentiation. Activation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) by secretory mammalian Ly-6 urokinase-type plasminogen activator receptor-associated protein 1 (SLURP-1) caused a significant increase in the expression levels of NF-κB, receptor activator of nuclear factor-kappa B ligand (RANKL), and the ratio of RANKL/osteoprotegerin (OPG). These effects were inhibited by alpha-bungarotoxin (α-BTX). Furthermore, the expression levels of RANKL/OPG were significantly reduced following inhibition of NF-κB. High-strength, dynamic positive pressure increased the expression of SLURP-1 and α7 nAChR in DDPSCs in the stable stage. These data indicated that mechanical stress stimulated the expression of SLURP-1 and α7 nAChR in DDPSCs. Additionally, SLURP-1 activated α7 nAChR, thereby upregulating the expression of NF-κB and enhancing its activity, thus regulating RANKL/OPG expression and affecting the ability of DDPSCs to influence osteoclastogenesis, which likely enhances root resorption and leads to the physiological loss of deciduous teeth.