The Role of BMP Signaling in Mediating Stimulatory Effects of FGF-FGFR Signaling on Odontoblast Differentiation in Dental Pulp

The Role of BMP Signaling in Mediating Stimulatory Effects of FGF-FGFR Signaling on Odontoblast Differentiation in Dental Pulp PDF Author: Karen Sagomonyants
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :

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Book Description
Odontoblast differentiation is dependent on multiple signaling molecules, including growth factors stored in the extracellular dentin matrix. Our previous studies have demonstrated that Fibroblast Growth Factor 2 (FGF2) exerted stage-specific effects on odontoblast differentiation in primary dental pulp cultures. FGF2 stimulated differentiation of functional odontoblasts expressing high levels of Dmp1 from early progenitors but inhibited the terminal differentiation of functional odontoblasts to fully differentiated odontoblasts expressing high levels of Dspp. These stimulatory effects involved activation of FGFR and ERK1/2, and increased levels of expression of Bmp2, Runx2, and Osx (components of BMP signaling) suggesting the involvement of BMP signaling in FGF2-induced Dspp expression. Therefore, the overall goal of the studies outlined in this thesis was to examine the role of BMP signaling in stimulatory effects of FGF signaling on odontoblast differentiation of dental pulp cells. We showed that BMP2 did not affect the extent of mineralization but rapidly (within ~12-24 hrs) stimulated expression of Dspp and intensity of DSPP-Cerulean transgene in a concentration-dependent manner without affecting the percentage of DSPP-Cerulean+ odontoblasts. In contrast to Dspp, BMP2 rapidly (within ~24-48 hrs) decreased expression of Dmp1, Bsp, DMP1-mCherry, and BSP-GFP in a concentration-dependent manner. Inhibition of the BMP and FGF signaling pathways by noggin and SU5402, respectively, did not have marked effects on the extent of mineralization but decreased expression of Dspp stimulated by these growth factors. These inhibitory effects were long-lasting and observed up to 14 days after removal of the growth factors. Additional experiments in primary bone marrow stromal cells cultures demonstrated that early and limited exposure to BMP2 did not affect mineralization but decreased expression of Dmp1, Bsp, and respective transgenes. Taken together, our results demonstrated that activation of the canonical BMP signaling pathway during the proliferation phase of in vitro growth resulted in significant increases in the expression of Dspp, and these increases were mediated via reciprocal interaction of the BMP and FGF signaling pathways. These data will further elucidate the perspectives of using both FGF2 and BMP2 in dentin regeneration applications.

The Role of BMP Signaling in Mediating Stimulatory Effects of FGF-FGFR Signaling on Odontoblast Differentiation in Dental Pulp

The Role of BMP Signaling in Mediating Stimulatory Effects of FGF-FGFR Signaling on Odontoblast Differentiation in Dental Pulp PDF Author: Karen Sagomonyants
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :

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Book Description
Odontoblast differentiation is dependent on multiple signaling molecules, including growth factors stored in the extracellular dentin matrix. Our previous studies have demonstrated that Fibroblast Growth Factor 2 (FGF2) exerted stage-specific effects on odontoblast differentiation in primary dental pulp cultures. FGF2 stimulated differentiation of functional odontoblasts expressing high levels of Dmp1 from early progenitors but inhibited the terminal differentiation of functional odontoblasts to fully differentiated odontoblasts expressing high levels of Dspp. These stimulatory effects involved activation of FGFR and ERK1/2, and increased levels of expression of Bmp2, Runx2, and Osx (components of BMP signaling) suggesting the involvement of BMP signaling in FGF2-induced Dspp expression. Therefore, the overall goal of the studies outlined in this thesis was to examine the role of BMP signaling in stimulatory effects of FGF signaling on odontoblast differentiation of dental pulp cells. We showed that BMP2 did not affect the extent of mineralization but rapidly (within ~12-24 hrs) stimulated expression of Dspp and intensity of DSPP-Cerulean transgene in a concentration-dependent manner without affecting the percentage of DSPP-Cerulean+ odontoblasts. In contrast to Dspp, BMP2 rapidly (within ~24-48 hrs) decreased expression of Dmp1, Bsp, DMP1-mCherry, and BSP-GFP in a concentration-dependent manner. Inhibition of the BMP and FGF signaling pathways by noggin and SU5402, respectively, did not have marked effects on the extent of mineralization but decreased expression of Dspp stimulated by these growth factors. These inhibitory effects were long-lasting and observed up to 14 days after removal of the growth factors. Additional experiments in primary bone marrow stromal cells cultures demonstrated that early and limited exposure to BMP2 did not affect mineralization but decreased expression of Dmp1, Bsp, and respective transgenes. Taken together, our results demonstrated that activation of the canonical BMP signaling pathway during the proliferation phase of in vitro growth resulted in significant increases in the expression of Dspp, and these increases were mediated via reciprocal interaction of the BMP and FGF signaling pathways. These data will further elucidate the perspectives of using both FGF2 and BMP2 in dentin regeneration applications.

Insight Into Stage-specific Effects of Fibroblast Growth Factor Signaling on Dental Pulp Cells

Insight Into Stage-specific Effects of Fibroblast Growth Factor Signaling on Dental Pulp Cells PDF Author: Karen Sagomonyants
Publisher:
ISBN:
Category :
Languages : en
Pages : 818

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Book Description


Dental Stem Cells: Regenerative Potential

Dental Stem Cells: Regenerative Potential PDF Author: Barbara Zavan
Publisher: Humana Press
ISBN: 3319332996
Category : Science
Languages : en
Pages : 288

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Book Description
This book focuses on the basic aspects of dental stem cells (DSCs) as well as their clinical applications in tissue engineering and regenerative medicine. It opens with a discussion of classification, protocols, and properties of DSCs and proceeds to explore DSCs within the contexts of cryopreservation; epigenetics; pulp, periodontal, tooth, bone, and corneal stroma regeneration; neuronal properties, mesenchymal stem cells and biomaterials; and as sources of hepatocytes for liver disease treatment. The fifteen expertly authored chapters comprehensively examine possible applications of DSCs and provide invaluable insights into mechanisms of growth and differentiation. Dental Stem Cells: Regenerative Potential draws from a wealth of international perspectives and is an essential addition to the developing literature on dental stem cells. This installment of Springer’s Stem Cell Biology and Regenerative Medicine series is indispensable for biomedical researchers interested in bioengineering, dentistry, tissue engineering, regenerative medicine, cell biology and oncology.

Seltzer and Bender's Dental Pulp

Seltzer and Bender's Dental Pulp PDF Author: Kenneth M. Hargreaves
Publisher: Quintessence Publishing (IL)
ISBN: 9780867154801
Category : Dental Pulp / physiology
Languages : en
Pages : 0

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Book Description
"Nearly three decades ago, Samuel Seltzer and I. B. Bender pioneered the concept of developing biologically based recommendations for the clinical practice of endodontics and restorative dentistry. This concept was the cornerstone of their classic textbook, The Dental Pulp. Seltzer and Bender's Dental Pulp represents the evolution of that book and of the philosophical principles on which it was based. Today we know that pulp tissue plays a central role in both local and systemic health. This book presents the latest research on the dental pulp and its interaction with other tissues. Each chapter provides an introduction to its major themes for the busy clinician or dental student, as well as a set of biologically based clinical recommendations for restorative and endodontic procedures. "--Publisher.

Bone and Development

Bone and Development PDF Author: Felix Bronner
Publisher: Springer Science & Business Media
ISBN: 1848828225
Category : Medical
Languages : en
Pages : 321

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Book Description
This, the sixth volume in a series of reviews centered on a single major topic in osteopathy, examines pediatric bone development. It covers problematic aspects from basic skeletal growth to tooth mineralization, and synthesizes theory and practice.

Gastrointestinal Physiology

Gastrointestinal Physiology PDF Author: Menizibeya Osain Welcome
Publisher: Springer
ISBN: 3319910566
Category : Medical
Languages : en
Pages : 1037

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Book Description
This book offers one of the most comprehensive reviews in the field of gastrointestinal (GI) physiology, guiding readers on a journey through the complete digestive tract, while also highlighting related organs and glandular systems. It is not solely limited to organ system physiology, and related disciplines like anatomy and histology, but also examines the molecular and cellular processes that keep the digestive system running. As such, the book provides extensive information on the molecular, cellular, tissue, organ, and system levels of functions in the GI system. Chapters on the roles of the gut as an endocrine, exocrine and neural organ, as well as its microbiome functions, broaden readers’ understanding of the multi-organ networks in the human body. To help illustrate the interconnections between the physiological concepts, principles and clinical presentations, it outlines clinical examples such as pathologies that link basic science with clinical practice in special “clinical correlates” sections. Covering both traditional and contemporary topics, it is a valuable resource for biomedical students, as well as healthcare and scientific professionals.

Genetics of Bone Biology and Skeletal Disease

Genetics of Bone Biology and Skeletal Disease PDF Author: Rajesh V. Thakker
Publisher: Academic Press
ISBN: 0128041986
Category : Science
Languages : en
Pages : 880

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Book Description
Genetics of Bone Biology and Skeletal Disease, Second Edition, is aimed at students of bone biology and genetics and includes general introductory chapters on bone biology and genetics. More specific disease orientated chapters comprehensively summarize the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder. The book is organized into five sections that each emphasize a particular theme, general background to bone biology, general background to genetics and epigenetics, disorders of bone and joint, parathyroid and related disorders, and vitamin D and renal disorders. The first section is specifically devoted to providing an overview of bone biology and structure, joint and cartilage biology, principles of endocrine regulation of bone, and the role of neuronal regulation and energy homeostasis. The second section reviews the principles and progress of medical genetics and epigenetics related to bone disease, including genome-wide association studies (GWAS), genomic profiling, copy number variation, prospects of gene therapy, pharmacogenomics, genetic testing and counseling, as well as the generation and utilizing of mouse models. The third section details advances in the genetics and molecular biology of bone and joint diseases, both monogenic and polygenic, as well as skeletal dysplasias, and rarer bone disorders. The fourth section highlights the central role of the parathyroids in calcium and skeletal homeostasis by reviewing the molecular genetics of: hyperparathyroidism, hypoparathyrodism, endocrine neoplasias, and disorders of the PTH and calcium-sensing receptors. The fifth section details molecular and cellular advances across associated renal disorders such as vitamin D and rickets. - Identifies and analyzes the genetic basis of bone disorders in humans and demonstrates the utility of mouse models in furthering the knowledge of mechanisms and evaluation of treatments - Demonstrates how the interactions between bone and joint biology, physiology, and genetics have greatly enhanced the understanding of normal bone function as well as the molecular pathogenesis of metabolic bone disorders - Summarizes the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder

Dento/Oro/Craniofacial Anomalies and Genetics

Dento/Oro/Craniofacial Anomalies and Genetics PDF Author: Agnes Bloch-Zupan
Publisher: Elsevier
ISBN: 0124160387
Category : Medical
Languages : en
Pages : 265

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Book Description
Dental defects may be the physical expression of genetic defects, and so they can often be seen in a variety of syndromes associated with malformations of organs. However, dental defects are often not recognized, identified, nor characterised despite representing a possible diagnostic sign for an undiagnosed condition. This book addresses this gap by providing an understanding of dental genetics and its developmental biology counterpart. With approximately seventy well-illustrated examples, the authors present the clinical oro-facial manifestations accompanying various syndromes, providing the necessary knowledge for diagnostic purposes, as well as giving insight into recent development for each specific condition. The clarity and format of this book make it an ideal support guide both in the clinic and while conducting research. Comprehensive examination of dento/oro/craniofacial anomalies Well-illustrated examples Presented in a compact, easy to use format

Human Embryology

Human Embryology PDF Author: William James Larsen
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 516

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Book Description
An introduction to the basic concepts and principles which underlie the first eight weeks of human development. Each chapter includes revision-orientated summary boxes, as well as sections detailing clinical examples relevant to the topic.

The Neural Crest in Development and Evolution

The Neural Crest in Development and Evolution PDF Author: Brian K. Hall
Publisher: Springer Science & Business Media
ISBN: 1475730640
Category : Science
Languages : en
Pages : 322

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Book Description
A discussion of the neural crest and neural crest cells, dealing with their discovery, their embryological and evolutionary origins, their cellular derivatives - in both agnathan and jawed vertebrates or gnathostomes - and the broad topics of migration and differentiation in normal development. The book also considers what goes wrong when development is misdirected by mutations, or by exposure of embryos to exogenous agents such as drugs, alcohol, or excess vitamin A, and includes discussions of tumours and syndromes and birth defects involving neural crest cells.