The Science of Marine Protected Areas (3rd edition, Mediterranean)

The main purpose of the booklet is to present the latest scientific information about the effects of MPAs in the Mediterranean in order to inform current management dialogues. This is particularly relevant given the increasing legislative frameworks and political initiatives to implement networks of MPAs in countries across the Mediterranean Sea. Importantly, this Edition does much more than simply tailor the earlier content for the Mediterranean region. The edition update the basic content of the booklet, drawing on the wealth of new published scientific literature, highlighting case studies from the Mediterranean Sea

The role of adipokines in periodontal infection and healing.

Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity-related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases

Loosening of the fixing screw in single implant crowns: predisposing factors, prevention and treatment options

The problem of technical complications in implants and implant-supported restorations has existed for decades. The most frequent complication is the loosening of the fixing screw, which although is not catastrophic, if it occurs repeatedly, it may affect the success of the implant therapy and the patient satisfaction. Factors that affect the frequency of prosthetic complications include: the implant-abutment connection, para-functional habits, cantilevers, and the type of restoration. Regarding the implant-abutment connection, the first systems were those with an external hexagon. Because of their small height and the disadvantages that this entails, other connection types were developed, such as those of hexagonal and conical connection, which decreased the complication rates, including the loosening of the fixing screw. On the dilemma “cement- or screw-retained restoration”, the choice depends on biological, technical, and aesthetic factors. Cement-retained restorations are simpler in construction with lower cost and clinicians are more familiar with the clinical procedure. On the other side, if the fixing screw of the abutment is loosened in a cement-retained restoration, it may be a difficult and demanding clinical task to fix this prosthetic complication. Screw-retained restorations are more prone to loosening of the fixing screw, but allow easy retrievability and repair. Their use however, is often restricted because of diverting or unfavorable inclination of the alveolar ridge and the implant. The aim of this article was to present clinical solutions for the complication of screw-loosening through clinical examples and discuss the factors that may predispose to its occurrence. CLINICAL SIGNIFICANCE: The problem of technical complications in implants and implant-supported restorations has existed for decades. The most frequent complication is the loosening of the fixing screw which, although is not catastrophic, if it occurs repeatedly, it may affect the success of the implant therapy and the patient satisfaction. Factors that affect the frequency of prosthetic complications include: the implant-abutment connection, para-functional habits, cantilevers and the type of restoration. The treatment options for the clinician are limited but certain preventing measures during construction of the restoration may be helpful to overcome this clinical problem. © 2017 Wiley Periodicals, Inc

PEEK High Performance Polymers: A Review of Properties and Clinical Applications in Prosthodontics and Restorative Dentistry

Various materials have been used over time in prosthetic dentistry. However, due to the evolution of science and knowledge, new materials are being brought to the forefront. Polyether ether ketone (PEEK) is a polymer with many potential applications in dentistry. The use of PEEK has become increasingly more common in dental practice; its favorable properties have made it a compelling alternative biomaterial in restorative dentistry. The current trend is moving towards the use of metal-free restorations and biomaterials which exhibit advanced properties in the complex oral environment. This review paper presents and summarizes clinical applications of PEEK in contemporary dentistry. Copyright© 2019 Dennis Barber Ltd

Regulation of matrix metalloproteinase-1 by Filifactor alocis in human gingival and monocytic cells

Objectives: Periodontitis is a highly prevalent chronic inflammatory disease caused by periodontopathogens, such as Filifactor alocis. This study sought to examine the matrix metalloproteinase (MMP)-1 synthesis by monocytic and fibroblastic cells in response to F. alocis and to unravel the underlying cellular mechanisms. Material and methods: Gingival biopsies from periodontally healthy and periodontitis individuals were analyzed for the presence of F. alocis and MMP-1 by RT-PCR. Human gingival fibroblastic (HGF-1) and monocytic (THP-1) cells were stimulated with F. alocis in the presence and absence of a blocking toll-like receptor (TLR)2 antibody or specific inhibitors against MAPKs. MMP-1 expression and protein levels were studied by RT-PCR and ELISA, respectively. Results: F. alocis was highly prevalent in biopsies from periodontitis patients but barely present in the healthy gingiva. Significantly higher MMP-1 expression levels were found in the inflamed gingiva as compared with healthy biopsies. F. alocis caused a significant and dose-dependent MMP-1 upregulation in both cells. The stimulatory effect of F. alocis on MMP-1 was TLR2- and MAPK-dependent and more pronounced on THP-1 cells as compared with HGF-1 cells. Conclusions: Our results demonstrate that F. alocis and MMP-1 are more prevalent at periodontitis sites. Additionally, our study provides original evidence that F. alocis can stimulate MMP-1 production by fibroblastic and monocytic cells, suggesting that F. alocis may contribute to periodontal breakdown through MMP-1. Clinical relevance: F. alocis and MMP-1 are linked to each other and key players in periodontitis, which may have significant implications for future diagnostic and treatment strategies. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Mechanosensor polycystin-1 potentiates differentiation of human osteoblastic cells by upregulating Runx2 expression via induction of JAK2/STAT3 signaling axis

Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1 involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with intracellular pathways and transcription factors to regulate cell function. Here we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in mechanically stimulated human osteoblastic cells, leading to transcriptional induction of Runx2 gene, a master regulator of osteoblastic differentiation. Primary osteoblast-like PC1-expressing cells subjected to mechanical-stretching exhibited a PC1-dependent increase of the phosphorylated(p)/active form of JAK2. Specific interaction of PC1-CT with pJAK2 was observed after stretching while pre-treatment of cells with PC1 (anti-IgPKD1) and JAK2 inhibitors abolished JAK2 activation. Consistently, mechanostimulation triggered PC1-mediated phosphorylation and nuclear translocation of STAT3. The nuclear phosphorylated(p)/DNA-binding competent pSTAT3 levels were augmented after stretching followed by elevated DNA-binding activity. Pre-treatment with a STAT3 inhibitor either alone or in combination with anti-IgPKD1 abrogated this effect. Moreover, PC1-mediated mechanostimulation induced elevation of Runx2 mRNA levels. ChIP assays revealed direct regulation of Runx2 promoter activity by STAT3/Runx2 after mechanical-stretching that was PC1-dependent. Our findings show that mechanical load upregulates expression of Runx2 gene via potentiation of PC1–JAK2/STAT3 signaling axis, culminating to possibly control osteoblastic differentiation and ultimately bone formation. © 2016, Springer International Publishing

Role of cathepsin S In periodontal wound healing-an in vitro study on human PDL cells

Background: Cathepsin S is a cysteine protease, which is expressed in human periodontal ligament (PDL) cells under inflammatory and infectious conditions. This in vitro study was established to investigate the effect of cathepsin S on PDL cell wound closure. Methods: An in vitro wound healing assay was used to monitor wound closure in wounded PDL cell monolayers for 72h in the presence and absence of cathepsin S. In addition, the effects of cathepsin S on specific markers for apoptosis and proliferation were studied at transcriptional level. Changes in the proliferation rate due to cathepsin S stimulation were analyzed by an XTT assay, and the actions of cathepsin S on cell migration were investigated via live cell tracking. Additionally, PDL cell monolayers were treated with a toll-like receptor 2 agonist in the presence and absence of a cathepsin inhibitor to examine if periodontal bacteria can alter wound closure via cathepsins. Results: Cathepsin S enhanced significantly the in vitro wound healing rate by inducing proliferation and by increasing the speed of cell migration, but had no effect on apoptosis. Moreover, the toll-like receptor 2 agonist enhanced significantly the wound closure and this stimulatory effect was dependent on cathepsins. Conclusions: Our findings provide original evidence that cathepsin S stimulates PDL cell proliferation and migration and, thereby, wound closure, suggesting that this cysteine protease might play a critical role in periodontal remodeling and healing. In addition, cathepsins might be exploited by periodontal bacteria to regulate critical PDL cell functions. © 2018 The Author(s)

Damage-regulated autophagy modulator 1 in oral inflammation and infection.

OBJECTIVES Damage-regulated autophagy modulator (DRAM) 1 is a p53 target gene with possible involvement in oral inflammation and infection. This study sought to examine the presence and regulation of DRAM1 in periodontal diseases. MATERIAL AND METHODS In vitro, human periodontal ligament fibroblasts were exposed to interleukin (IL)-1β and Fusobacterium nucleatum for up to 2 days. The DRAM1 synthesis and its regulation were analyzed by real-time PCR, immunocytochemistry, and ELISA. Expressions of other autophagy-associated genes were also studied by real-time PCR. In vivo, synthesis of DRAM1 in gingival biopsies from rats and patients with and without periodontal disease was examined by real-time PCR and immunohistochemistry. For statistics, ANOVA and post-hoc tests were applied (p < 0.05). RESULTS In vitro, DRAM1 was significantly upregulated by IL-1β and F. nucleatum over 2 days and a wide range of concentrations. Additionally, increased DRAM1 protein levels in response to both stimulants were observed. Autophagy-associated genes ATG3, BAK1, HDAC6, and IRGM were also upregulated under inflammatory or infectious conditions. In vivo, the DRAM1 gene expression was significantly enhanced in rat gingival biopsies with induced periodontitis as compared to control. Significantly increased DRAM1 levels were also detected in human gingival biopsies from sites of periodontitis as compared to healthy sites. CONCLUSION Our data provide novel evidence that DRAM1 is increased under inflammatory and infectious conditions in periodontal cells and tissues, suggesting a pivotal role of DRAM1 in oral inflammation and infection. CLINICAL RELEVANCE DRAM1 might be a promising target in future diagnostic and treatment strategies for periodontitis

Role of Cathepsin S in Periodontal Inflammation and Infection

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis. © 2017 S. Memmert et al