Emi Shimizu

Rutgers, The State University of New Jersey | Rutgers · Oral Biology

Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators of dental pulp cell (DPC) mineralisation processes. Currently, there is a paucity of information regarding the nature of histone modification and HDAC expression in the dentine–pul...

Point of care (POC) diagnostic devices provide a method for rapid accurate identification of disease through analysis of biologically relevant substances. This review focuses on the utility of POC testing for early detection of periodontitis, a critical factor in treating the disease. Accessing the oral cavity for biological sampling is less invasi...

MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine–tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO and wild-...

This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that...

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the G...

The rise of antibiotic resistant bacteria due to overuse and misuse of antibiotics in medicine and dentistry is a growing concern. New approaches are needed to combat antibiotic resistant (AR) bacterial infections. There are a number of methods available and in development to address AR infections. Dentists conventionally use chemicals such as chlo...

Matrix-metalloproteinase-13 (MMP13) is important for bone formation and remodeling; however, its role in tooth development remains unknown. To investigate this, MMP13-knockout (Mmp13 −/− ) mice were used to analyze phenotypic changes in the dentin–pulp complex, mineralization-associated marker-expression, and mechanistic interactions. Immunohistoch...

For assessing the adequacy of vital pulp therapy for an inflamed pulp, the use of non-invasive diagnostic tools is necessary to avoid further damage to the teeth. Detection of biomarkers that are indicative of the inflammatory status in pulp can be a promising tool for this purpose. These biomarkers need to be reliably correlated with pulpal inflam...

Introduction Diabetes mellitus (DM) is a complex multisystemic disorder that affects an estimated 21 million Americans. No studies have evaluated the association of DM with the prevalence of each pulpal diagnosis. The objective of this study is to compare the prevalence of each pulp diagnosis including symptomatic irreversible pulpitis (SIP), asymp...

The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established met...

<p class = "Abstract" style = "margin: 0 cm; line-height: 32px; font-size: 12 pt; font-family: "Times New Roman", serif; color: rgb(0, 0, 0); "> The carious process leads to inflammation of pulp tissue. Current care options include root canal treatment or apexification. These procedures, however, result in the loss of tooth vitality, sensitivity, a...

Enhancer of zeste homolog 2 (EZH2) is the catalytic core of polycomb repressive complex 2 (PRC2), which primarily methylates lysine 27 on histone H3 (H2K27me3), generating transcriptionally suppressed heterochromatin. Since EZH2 suppresses expression of genes involved in dentin formation, we examined the role of EZH2 in tooth development. Intriguin...

Orofacial pain is a universal predicament, afflicting millions of individuals worldwide. Research on the molecular mechanisms of orofacial pain has predominately focused on the role of neurons underlying nociception. However, aside from neural mechanisms, non-neuronal cells, such as Schwann cells and satellite ganglion cells in the peripheral nervo...

Patients with type 1 diabetes mellitus (T1DM) exhibit reduced bone mineral density (BMD) and significant increases in fracture risk. Changes in BMD are attributed to blunted osteoblast activity and inhibited bone remodeling, but these cannot fully explain the impaired bone integrity in T1DM. Our goal was to determine the cellular mechanisms that co...

Angiogenesis is critical for tissue healing and regeneration. Promoting angiogenesis in materials implanted within dental pulp after pulpectomy is a major clinical challenge in endodontics. We demonstrate the ability of acellular self-assembling peptide hydrogels to create extracellular matrix mimetic architectures that guide in vivo development of...

If dental caries (or tooth decay) progresses without intervention, the infection will advance through the dentine leading to severe pulpal inflammation (irreversible pulpitis) and pulp death. The current management of irreversible pulpits is generally root-canal-treatment (RCT), a destructive, expensive, and often unnecessary procedure, as removal...

The aim of regenerative endodontics is to replace injured or infected structures, including root and crown dentine as well as cells in the pulp-dentine complex. Two strategies, cell-homing-based and cell-based regenerative strategies, are available for this purpose. In cell-homing-based regenerative strategies, the patient’s endogenous cells undert...

Purpose of Review To summarize current views on the role and therapeutic potential of growth factors (GFs) within endodontic cell homing. Recent Findings Cell homing/revitalization techniques aim to regenerate dentin and pulp using endogenous cells. Clinically, revitalization has successfully created new vital tissue in necrotic permanent teeth wi...

Current standard of care for treating infected dental pulp, root canal therapy, retains the physical properties of the tooth to a large extent, but does not aim to rejuvenate the pulp tissue. Tissue-engineered acellular biomimetic hydrogels have great potential to facilitate the regeneration of the tissue through the recruitment of autologous stem...

Eph receptors belong to a subfamily of receptor tyrosine kinases that are activated by membrane-spanning ligands called ephrins. Previously, we demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic differentiation from dental pulp cells (DPCs) in vitro. The goal of this study was to identify the molecular mechanisms regu...

Direct application of histone-deacetylase-inhibitors (HDACis) to dental pulp cells (DPCs) induces chromatin changes, promoting gene expression and cellular-reparative events. We have previously demonstrated that HDACis (Valproic acid, Trichostatin A) increase mineralization in dental papillae-derived cell-lines and primary DPCs by stimulation of de...

PTH is the only current anabolic treatment for osteoporosis in the USA. PTH stimulates expression of matrix metalloproteinase 13 (MMP13) in bone. Sirtuin 1 (SIRT1), an NAD-dependent deacetylase, participates in a variety of human diseases. Here we identify a role for SIRT1 in the action of PTH in osteoblasts. We observed increased Mmp13 mRNA expres...

Histone deacetylases (HDACs) are crucial regulators of gene expression in transcriptional co-repressor complexes. Previously, we reported that HDAC4 was a basal repressor of matrix metalloproteinase-13 (MMP-13) transcription and parathyroid hormone (PTH) regulates HDAC4 to control MMP-13 promoter activity through dissociation from Runx2. Here, we s...

Mechanical debridement plays an important role in eliminating intracanal bacteria, such as biofilm on the canal walls and bacteria in the dentinal tubules. Mechanical debridement is not recommended for root canal disinfection in revascularization/revitalization therapy. Here we report a failed revascularization/revitalization case, which could be d...

Calcium hydroxide is used in direct pulp capping of uncontaminated exposed vital pulps caused by mechanical or traumatic injury. Calcium hydroxide creates a high alkaline pH environment and initiates a mineralized tissue formation in the pulp. The exact mechanism by which calcium hydroxide induces the reparative dentin formation is unknown. Because...

Parathyroid hormone (PTH) has a significant role as an anabolic hormone in bone when administered by intermittent injection. Previous microarray studies in our laboratory have shown that the most highly regulated gene, monocyte chemoattractant protein-1 (MCP-1), is rapidly and transiently induced when hPTH(1-34) is injected intermittently in rats....

Revitalization procedures have been widely used for the treatment of immature permanent teeth with apical periodontitis. The treatment procedures appear to be capable of encouraging continued root development and thickening of the canal walls. The nature of tissues formed in the canal space and at the root apex after revitalization has been shown h...

Objective: Calcium hydroxide has been used in direct pulp capping of uncontaminated exposed vital pulps. Calcium hydroxide causes high alkaline pH and then initiates dentin formation. This is followed by the reparative process, which includes migration and proliferation of pulp stem cells. The exact mechanism by which calcium hydroxide induces th...

Objectives: Parathyroid hormone (PTH) is a major regulator of calcium metabolism and has a clear anabolic effect to stimulate trabecular bone formation, by directly increasing the proliferation and differentiation of osteoblast while inhibiting their apoptosis. Our previous data had shown intermittent PTH(1-34) administration increased Wnt-4 gene e...

Background: Matrix metalloproteinase-13 (MMP-13) is an important enzyme for the modulation of bone turnover and gingival recession. Elevated levels of MMP-13 are associated with alveolar bone resorption, periodontal ligament breakdown, and gingival attachment loss, which are the clinical symptoms of periodontal disease. Evidence continues to sugge...

Histological studies of immature human permanent necrotic teeth with or without apical periodontitis after revascularization have not been reported. This case report describes the histological findings of tissue formed in the canal space of an immature permanent tooth #9 with irreversible pulpitis without apical periodontitis after revascularizatio...

Objective: Bisphosphonates are therapeutic agents for the treatment of postmenopausal osteoporosis. Although they have been associated with delayed healing in injured tissues, resulting in inappropriate femoral fractures and osteonecrosis of the jaw (ONJ), the pathophysiological mechanisms involved are not clear. Our hypothesis is that alendronate,...

Bisphosphonates are therapeutic agents in the treatment of post-menopausal osteoporosis. Although they have been associated with delayed healing in injured tissues, inappropriate femoral fractures, and osteonecrosis of the jaw (ONJ), the pathophysiological mechanisms involved are not clear. Our hypothesis is that alendronate, a member of the N-cont...

The epidermal growth factor receptor (EGFR) and its ligands regulate key processes of cell biology, such as proliferation, survival, differentiation, migration, and tumorigenesis. We previously showed that, EGFR signaling pathway is an important bone regulator and it primarily plays an anabolic role in bone metabolism. In this study, we demonstrate...

Parathyroid hormone (PTH) is a hormone regulating bone remodeling through its actions on both bone formation and bone resorption. Previously we reported that PTH induces matrix metalloproteinase-13 (MMP-13) transcription in osteoblastic cells. Here, we show that histone deacetylase 4 (HDAC4) interacts with Runx2, binds the MMP-13 promoter, and supp...

PTH regulates transcription of a number of genes involved in bone remodeling and calcium homeostasis. We have previously shown that the matrix metalloproteinase-13 (MMP-13) gene is induced by PTH in osteoblastic cells as a secondary response through the protein kinase A pathway requiring the runt domain and activator protein 1 binding sites of the...

Matrix metalloproteinase-13 (MMP-13) plays a critical role in parathyroid hormone (PTH)-induced bone resorption. PTH acts via protein kinase A (PKA) to phosphorylate and stimulate the transactivation of Runx2 for MMP-13 promoter activation. We show here that PTH stimulated Runx2 phosphorylation in rat osteoblastic cells. Runx2 was phosphorylated on...

Interleukin-18 (IL-18) can regulate osteoblast and osteoclast function. We have identified, using cDNA microarray technology, that IL-18 expression is increased in UMR 106-01 rat osteoblastic cells in response to parathyroid hormone (PTH) treatment. Confirmation of these data using real-time reverse transcription-PCR showed that steady-state levels...

This chapter surveys the current knowledge of the proteinases expressed in bone. Although previously the osteoclast was considered to be the main producer of proteinases in bone, it has become increasingly clear that osteoblasts play a significant role in the production of many of these proteinases. Based on the structure and the catalytic mechanis...

Parathyroid hormone (PTH) functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We have already shown that PTH stimulates the expression of matrix metalloproteinase-13 (MMP-13), which is responsible for degrading components of extracellular matrix. We have hypothesized that histone deacetylases (HDACs) are...

Bone sialoprotein (BSP) is a noncollagenous protein of the mineralized bone extracellular matrix. We here report that FGF2 and cAMP act synergistically to stimulate BSP gene expression. Treatment of ROS 17/2.8 cells with either 10 ng/ml FGF2 or 1 microM FSK for 6 h resulted in 5.4- and 8.2-fold increases, respectively, in the levels of BSP mRNA. Ho...

Bone sialoprotein (BSP), an early marker of osteoblast differentiation. Whereas physical forces may play an important role in the regulation of bone cell function, little is known about how cells are able to sense mechanical loads. Chlorpromazine, a tranquilizing agent for treatments of psychiatric disorders, mimics hypotonic stress and causes memb...

Lipopolysaccharide (LPS) is a major mediator of inflammatory responses in periodontal disease that inhibits bone formation and stimulates bone resorption. To determine the molecular mechanisms involved in the suppression of bone formation, we have analyzed the effects of LPS on BSP gene expression. Bone sialoprotein (BSP) is a mineralized tissue-sp...

Amelogenins are a complex mixture of hydrophobic proteins that are the major organic component of developing enamel. The principal function of the amelogenins and their degradation products has been assigned to structural roles in creating the space and milieu for promoting enamel mineralization. Enamel matrix derivative (EMD) has been used clinica...

Periodontitis is a common inflammatory disease causing destruction of periodontal tissues. It is a multifactor disease involving genetic factors and oral environmental factors. To determine genetic risk factors associated with aggressive periodontitis or severe chronic periodontitis, single nucleotide polymorphisms (SNPs) in multiple candidate gene...

Bone sialoprotein (BSP) is a sulfated and phosphorylated glycoprotein found almost exclusively in mineralized connective tissues. Recent studies on the developmental expression of BSP mRNA and temporo-spatial appearance of the protein during bone formation in vivo and in vitro have demonstrated that BSP is expressed by differentiated osteoblasts, a...

Enamel matrix derivative (EMD) has recently been developed for use as a periodontal regenerative treatment. While EMD is believed to induce regeneration of periodontal tissue, the precise mechanism is not known. Bone sialoprotein (BSP), an early phenotypic marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite...

Tumor necrosis factor‐alpha (TNF‐α) is a major mediator of inflammatory response in many diseases. It inhibits bone formation and stimulates bone resorption. To determine the molecular mechanisms involved in the regulation of gene expression of osteoblast‐like cells, we analyzed the effects of TNF‐α on the human osteosarcoma cell line Saos2. We use...

Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite during de novo bone formation. Prostaglandin E2 (PGE2) has anabolic effects on proliferation and differentiation of osteoblasts via diverse signal transduction systems. Because PGE2 increases the proportion of functional o...

Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite during de novo bone formation. Basic fibroblast growth factor (FGF2) is recognized as a potent mitogen for a variety of mesenchymal cells. In skeletal tissues, FGF2 produced by osteoblasts accumulates in the bone matrix an...

Bradykinin (1 microM) and histamine (100 microM) evoked an initial transient increase and a subsequent sustained increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in fura-2-loaded human gingival fibroblasts, which may be attributed to Ca(2+) release from intracellular stores and Ca(2+) entry from extracellular sites, respectively. In fib...

Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite during de novo bone formation. Basic fibroblast growth factor (FGF2) is recognized as a potent mitogen for a variety of mesenchymal cells. In skeletal tissues, FGF2 produced by osteoblasts accumulates in the bone matrix an...

Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of inflammatory responses in many diseases that inhibits bone formation and stimulates bone resorption. To determine molecular mechanisms involved in the suppression of bone formation we have analyzed the effects of TNF-alpha on BSP gene expression. Bone sialoprotein (BSP) is a mineralized...

Nuclear factor kappaB (NFkappaB) is a transcription factor and plays a key role in the expression of several genes involved in the inflammatory process. Cyclooxygenase (COX) is the key regulatory enzyme of the prostaglandin/eicosanoid synthetic pathway. COX-2 is a highly inducible enzyme by proinflammatory cytokines, of which gene expression is reg...

Bone sialoprotein (BSP) is a major noncollagenous protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite. Recent studies have shown that BSP is also expressed by osteotropic cancers suggesting BSP might play a role in the pathogenesis of bone metastases. The present study investigates regul...

Bone sialoprotein (BSP) is a sulfated and phosphorylated glycoprotein, found almost exclusively in mineralized connective tissues, that may function in the nucleation of hydroxyapatite crystals. We have found that expression of BSP in osteoblastic ROS 17/2.8 cells is stimulated by fibroblast growth factor 2 (FGF2), a potent mitogen for mesenchymal...

The immediate-early cyclooxygenase-2 (COX-2) gene encodes an inducible prostaglandin synthase enzyme which is implicated in inflammatory and proliferative diseases. COX-2 is highly induced during cell activation by various factors, including mitogens, hormones and cytokines. Since pro-inflammatory cytokine IL-1beta has been shown to induce prostagl...

The immediate-early cyclooxygenase-2 (COX-2) gene encodes an inducible prostaglandin synthase enzyme which is implicated in inflammatory and proliferative diseases. COX-2 is highly induced during cell activation by various factors, including mitogens, hormones and cytokines. Since pro-inflammatory cytokine IL-1β has been shown to induce prostagland...