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Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone‐specific anabolic and anti‐inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress‐activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real‐time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF‐κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro‐inflammatory TNF‐α and NF‐κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF‐kB Inhibition.

Intestinal exocrine secretory cells, including Paneth and goblet cells, have a pivotal role in intestinal barrier function and mucosal immunity. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Therefore, identification and elucidation of key molecular mechanisms that regulate the development and function of these exocrine cells would be crucial for understanding of disease pathogenesis and discovery of new therapeutic targets. The Ufm1 conjugation system is a novel ubiquitin-like modification system that consists of Ufm1 (Ubiquitin modifier 1), Uba5 (Ufm1-activating enzyme, E1), Ufc1 (Ufm1-conjugating enzyme, E2) and poorly characterized Ufm1 E3 ligase(s). Recent mouse genetic studies have demonstrated its indispensable role in embryonic development and hematopoiesis. Yet its role in other tissues and organs remains poorly defined. In this study, we found that both Ufl1 and Ufbp1, two key components of the Ufm1 E3 ligase, were highly expressed in the intestinal exocrine cells. Ablation of either Ufl1 and Ufbp1 led to significant loss of both Paneth and goblet cells, which in turn resulted in dysbiotic microbiota and increased susceptibility to experimentally induced colitis. At the cellular and molecular levels, Ufbp1 deficiency caused elevation of endoplasmic reticulum stress and activation of the Unfolded Protein Response (UPR) and cell death program. Administration of small molecular chaperone partially prevented loss of Paneth cells caused by acute Ufbp1 deletion. Taken together, our results have provided unambiguous evidence for the crucial role of the Ufm1 E3 ligase in maintenance of intestinal homeostasis and protection from inflammatory diseases.

Periodontitis is characterized by pathological destruction of extracellular matrix (ECM) of periodontal tissues. Matrix metalloproteinases (MMPs) promote the occurrence and development of periodontitis by degrading almost all proteins of ECM. RECK (reversion-inducing-cysteine-rich protein with kazal motifs), a novel membrane-anchored inhibitor of MMPs, could regulate the expression of MMP-2 and MMP-9 at post-transcriptional level. The study was to investigate the expression of RECK in healthy and diseased human gingival tissues and to correlate it with the production of MMP-2 and MMP-9.Gingival biopsies were collected from chronic periodontitis patients and periodontally healthy control individuals. The protein and mRNA of RECK, MMP-2 and MMP-9 was determined by immunohistochemistry and semi-quantitative polymerase chain reaction analysis.The expression of RECK protein was mainly confined to the gingival epithelium in inflamed and non-inflamed gingival tissues. Expression of RECK was significantly lower in tissues from chronic periodontitis patients, while the positive expression levels of MMP-2 and MMP-9 in periodontitis specimens were significantly higher. RECK protein expression was negatively correlated to the expressions of MMP-2 and MMP-9 in periodontitis. Moreover, RECK mRNA was significanly lower in diseased gingiva than in healthy samples(P0.05), while MMP-2 and MMP-9 mRNAs were observed overexpressed in periodontal lesions, with no significant correlation between RECK and MMP-2/MMP-9 mRNA shown in periodontally diseased group.The expression of RECK in human healthy and diseased gingiva may contribute to periodontal physiological and pathological processes; low RECK expression may be associated with the enhanced MMP-2 and MMP-9 production in inflamed gingiva.

As an essential component of the innate immune system, Toll-like receptors (TLRs) are a family of well-recognized ligand-binding receptors found in various organisms and initiate host immune responses. Activation of TLRs signaling pathways lead to the induction of numerous genes that function in host defense. Baicalin is a natural compound from the dry raw root of Scutellaria baicalensis (S. baicalensis) and it has been found to exhibit several pharmaceutical actions, such as anti-inflammation, anti-tumor and antivirus. These biological activities are mainly related to the regulatory effect of baicalin on the host immune response. In this review, we provide an overview of the regulation of baicalin on TLRs signaling pathways in various pathological conditions, and highlight potential targets for the development of the regulatory effect of natural compound from traditional Chinese medicine on innate immune system.

Periodontal disease is a chronic inflammatory disease leading to destruction of periodontal tissues. As a local inflammation, periodontopathic bacterium, pro-inflammatory mediators, and local immune response play pivotal role in the progress of periodontal disease. Besides, cigarette smoke has long been associated with periodontal disease and tooth loss. Autophagy is an intracellular degradation process highly conserved from yeast to humans. As a lysosomal degradation pathway of self-digestion, it is critical for maintaining cells homeostasis and development. The role of autophagy has been investigated in oral diseases, such as oral cancer, periapical lesions, and oral candidiasis. Recently, increasing studies investigated the role of autophagy in periodontal disease. In this review, we try to illustrate the effect of autophagy on periodontal disease pathogenesis from 5 aspects: autophagy affects the intracellular infection and survival of bacteria; autophagy has an interaction with periodontal inflammation; autophagy is pivotal in periodontal cells biology and periodontal tissues destruction and reconstruction; autophagy can be induced by cigarette smoke; last but not least, autophagy may affect periodontal disease via endoplasmic reticulum stress.

Periodontal diseases are characterized by pathological destruction of extracellular matrix (ECM) of periodontal tissues. Matrix metalloproteinases (MMPs) are a significant part of the degradation of ECM. However, the regulation of MMPs expression level in periodontal diseases is as yet undetermined. RECK (reversion-inducing cysteine-rich protein with Kazal motifs), a novel membrane-anchored inhibitor of MMPs, could regulate the expressions of MMP-2, 9 and MT1-MMP as a cell surface-signaling molecule. Thus, we propose that RECK may play an important role in regulating MMPs in the ECM degradation of periodontal diseases. The RECK/MMPs signaling pathway could provide a new approach for prevention and treatment of RECK in periodontal diseases by blocking MMPs.