Michel Goldberg

Editor

The Dental Pulp

Biology, Pathology, and
Regenerative Therapies

123
The Dental Pulp
Michel Goldberg
Editor

The Dental Pulp

Biology, Pathology, and Regenerative
Therapies
Editor
Michel Goldberg, DDS, PhD
Department of Oral Biology
Institut National de la Sant et de la
Recherche Mdicale
Universit Paris Descartes
Paris
France

ISBN 978-3-642-55159-8 ISBN 978-3-642-55160-4 (eBook)

DOI 10.1007/978-3-642-55160-4
Springer Heidelberg New York Dordrecht London

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Preface

The dental pulp has the characteristic of being exclusively the nonmineral-
ized part of a mineralized tooth. This tissue is surrounded by a robust shell-
like complex structure that includes dentin and enamel in the crown and
cementum in the root. Like most connective tissues, the dental pulp is vascu-
larized and innervated, which constitute important functional differences
between the crown and the root. It is also a reservoir of structural fibroblasts
(named pulpoblasts long ago by Louis Baume). The pulp complexity is
increased by the presence of progenitors (or stem cells) implicated in pulp
repair and regeneration.
Inflammatory immune cells are concerned with the destruction of patho-
gens, cell debris (apoptotic bodies), and/or adverse molecules. Altogether,
the heterogeneous cell colonies restore the reparative functions of the dental
pulp and consequently the biological approaches of pulp therapies. As an
alternative for the surgical or chemical ablation of this tissue and for a limited
size of the lesion, pulp capping with biomolecules has been successful. In the
case of a more advanced dental destruction, it comes out nowadays that vital
pulp regeneration is our next goal. The formation/regeneration of an artificial
pulp may be followed by the construction of a homogeneous mineralization,
sealing the root canal.
For future prospects in pulp therapies, it is important to take into account
three major points: (1) Usually, the dental pulp is not mineralized, and some
specificities of its composition may explain why it remains a soft tissue. This
point should be further explored and clarified. (2) In a very few cases, the
pulp may eventually mineralize, namely, when genetic pathologies such as
dentinogenesis imperfecta or dentin dysplasia disturb the tissue. In this
respect, gene expression seems crucial for the understanding of such pro-
cesses. (3) It should also be noted that in the aging pulp, some loci initiate
gradually localized or diffuse mineralized areas. They also contribute to the
formation of laminated pulp stones. Eventually, mineral diffusion occurs and
totally fills the dental pulp.
Therefore, these different aspects lead to a series of questions: (1) Why, in
normal physiological conditions, does the dental pulp remain a nonminer-
alized tissue? (2) Why, in some pathological cases, does mineralization of the
dental pulp occur? Can we identify the factors that influence the mineraliza-
tion even if the pulp was initially a soft tissue? Different studies shed some
light on questions that are still open. As a matter of fact, the answers obtained
from pulp studies may also expand to other tissues and/or to ectopic

v
vi Preface

mineralization. We may expect some answers to these unanswered questions.

Atheroma plaques, atherosclerosis, skin, eyes, kidney stones or large areas of
mineralizations, and other pathological calcifications are still under examina-
tion. Identification of some extracellular matrix molecules may contribute to
identify which molecules are in the lead. They may be mineralization inhibi-
tors, as it is the case for 2HS glycoprotein. Indeed, enlarged dental pulps are
seen when DMP1 is mutated. In contrast, such studies can contribute to our
understanding of the role of other molecules or ECM peptides. They may
shed light on normal regulation or pathological processes leading to the ini-
tiation and development of pulp mineralization.
Finally, we should also pinpoint that dental caries lead to chronic or acute
pulp reactions. They may be limited and controlled or expand within the
totality of the pulp tissue. Alternatively, pulp necrosis may occur, or pulp
healing can be observed. For a long period of time, endodontic treatment was
the privileged therapy. Biotherapies or biological approaches with mineral
components (e.g., calcium hydroxide), ECM, or bioactive peptide-derived
molecules have substantially reinforced the cascade of events occurring in the
wounded pulp. The healing process involves stem cell recruitment, their pro-
liferation and differentiation, and ECM synthesis and secretion, altogether
contributing to pulp recovery. As a consequence of forming an artificial pulp,
pulp regeneration is occurring. In terms of biology, stem cells contribute to
the construction of a nonmineralized pulp. The pulp will further mineralize,
and the final step of pulp biotherapy mimicks what can be expected from an
endodontic substitute. Tooth engineering is a promising tool for the near
future, sealing the lumen of the pulp root.
The selection of the contributors to this book was based on their unani-
mously well-recognized knowledge in this field and on their important publi-
cations in the field of pulp biology or physiopathology. They have explored
new concepts, new areas of research, and consequences of new data, which
may have some impact on the future of pulp therapies. The list of authors that
contributed to this book is based mostly on the warm friendship developed
during hot discussions, drinking many glasses of beer or wine and exchang-
ing arguments on burning points in many international conferences. We were
delighted to be present in such meetings and to show our latest findings or
raise some discussions on unanswered points. We were most happy to meet
again or to become connected with new friends.
After all these years, some of the coauthors really became my closest
friends, and we became coconspirators. This is the case especially for Art
Veis, who is for me an older brother and a wonderful example of what should
be done through a life span. In this Noahs ark, I feel sometimes that I am in
a floating boat, ensuring our temporary survival in a scientific domain. It is
certainly the reason why in this ship full of friends, we have launchedif we
keep a certain sense of humorwhat may be called a solid friendship.
During all these years, altogether we have built a kind of family, and it is
a pleasure to be associated with a group of researchers forming, so to say, a
pulp knota new organizing center, which is reflected in this book.

Paris, France Michel Goldberg, DDS, PhD

Contents

Part I Pulp Biology

1 Pulp Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Sasha Dimitrova-Nakov and Michel Goldberg
2 Pulp Anatomy and Characterization of Pulp Cells. . . . . . . . . 13
Michel Goldberg
3 Pulp Extracellular Matrix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Arthur Veis and Michel Goldberg
4 Strategies for Tracking the Origin and Fate
of Odontoblasts and Pulp Cell Progenitors . . . . . . . . . . . . . . . 47
Mina Mina
5 Pulp Vascularization and Its Regulation
by the Microenvironment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Imad About
6 Dental Pulp Innervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Kaj Fried and Jennifer Lynn Gibbs
7 Inflammatory Processes in the Dental Pulp. . . . . . . . . . . . . . . 97
Paul R. Cooper and Anthony J. Smith
8 Pulp Aging: Fibrosis and Calcospherites. . . . . . . . . . . . . . . . . 113
Michel Goldberg

Part II Pulp Pathology

9 Pulp Inflammation: From the Reversible Pulpitis

to Pulp Necrosis During Caries Progression . . . . . . . . . . . . . . 125
Lars Bjrndal and Domenico Ricucci
10 Reactionary and Reparative Dentin-Like Structures. . . . . . . 141
Michel Goldberg
11 Genetic Alterations: Heritable Dentin Defects . . . . . . . . . . . . 155
Agns Bloch-Zupan
12 Pulp Reactions to Dental Materials . . . . . . . . . . . . . . . . . . . . . 169
Gottfried Schmalz

vii
viii Contents

13 Effects of Bisphenol A on the Dental Pulp . . . . . . . . . . . . . . . . 185

Michel Goldberg
14 Fluoride Effects on the Dentin-Pulp Complex . . . . . . . . . . . . 191
Yukiko Nakano and Pamela Den Besten

Part III Pulp Repair and Regeneration

15 Experimental In Vivo Approaches of Pulp Regeneration. . . . 203

Misako Nakashima and Koichiro Iohara
16 Pulp Stem Cells: Niches of Stem Cells . . . . . . . . . . . . . . . . . . . 219
Michel Goldberg
17 Regeneration of the Living Pulp. . . . . . . . . . . . . . . . . . . . . . . . 237
Tracy L. de Peralta and Jacques Eduardo Nr
18 Scaffolds for Pulp Repair and Regeneration . . . . . . . . . . . . . . 251
Kerstin M. Galler
19 Regenerative Endodontics: Regeneration or Repair? . . . . . . 267
Stephane Simon and Michel Goldberg

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Contributors

Imad About, PhD Aix-Marseille Universit, Centre National de la

Recherche Scientifique, Marseille, France
Lars Bjrndal, DDS, PhD Department of Odontology,
Section of Cariology and Endodontics/Pediatric and Clinical Genetics,
University of Copenhagen, Copenhagen, Denmark
Agns Bloch-Zupan, HDR, PhD, DDS Department of Sciences
Biologiques, Faculty of Dentistry, University of Strasbourg,
Strasbourg, France
Reference Center for Orodental Manifestations of Rare Diseases,
Ple de Mdecine et Chirurgie Bucco-Dentaires,
Hpitaux Universitaires de Strasbourg, Strasbourg, France
Institute of Genetics and Molecular and Cellular Biology,
INSERM, Illkirch, France
Eastman Dental Institute, UCL, London, UK
Paul R. Cooper, PhD Department of Oral Biology, School of Dentistry,
University of Birmingham, Birmingham, B4 6NN, UK
Pamela Den Besten, DDS, MS Division of Pediatric Dentistry,
Department of Orofacial Sciences, School of Dentistry,
University of California, San Francisco, San Francisco, CA, USA
Sasha Dimitrova-Nakov, DDS, PhD Department of Oral Biology,
Institut National de la Sant et de la Recherche Mdicale, Universit Paris
Descartes, Paris, France
Kaj Fried, DDS, PhD Department of Neuroscience,
Karolinska Institutet, Stockholm, Sweden
Kerstin M. Galler, DDS, PhD Department of Restorative Dentistry and
Periodontology, University Hospital Regensburg, Regensburg, Germany
Jennifer Lynn Gibbs, MAS, DDS, PhD Department of Endodontics,
New York University College of Dentistry, New York, NY, USA

ix
x Contributors

Michel Goldberg, DDS, PhD Department of Oral Biology,

Institut National de la Sant et de la Recherche Mdicale,
Universit Paris Descartes, Paris, France
Koichiro Iohara, DDS, PhD Department of Dental Regenerative
Medicine, Center of Advanced Medicine for Dental and Oral Diseases,
National Center for Geriatrics and Gerontology, Research Institute,
Obu, Japan
Mina Mina, DMD, MSD, PhD Division of Pediatric Dentistry,
School of Dental Medicine, University of Connecticut Health Center,
Farmington, CT, USA
Yukiko Nakano, DDS, PhD Department of Orofacial Sciences,
School of Dentistry, University of California, San Francisco,
San Francisco, CA, USA
Misako Nakashima, PhD, DDS Department of Dental
Regenerative Medicine, Center of Advanced Medicine for Dental
and Oral Diseases, National Center for Geriatrics and Gerontology,
Research Institute, Obu, Japan
Jacques Eduardo Nr, DDS, MS, PhD Department of Cariology,
Restorative Sciences, and Endodontics, University of Michigan,
Ann Arbor, MI, USA
Tracy L. de Peralta, DMD, PhD, MClinEd Department of Cariology,
Restorative Sciences, and Endodontics, University of Michigan,
Ann Arbor, MI, USA
Domenico Ricucci, MD, DDS Private Practice, Cetraro, Italy
Gottfried Schmalz, DDS, DMD, PhD Department of Operative
Dentistry and Periodontology, University Hospital Regensburg,
University Clinics, Regensburg, Germany
School of Dental Medicine - ZMK Bern, University of Bern, Switzerland
Stphane Simon, DDS, PhD Department of Oral Biology
and Endodontics, Dental School of the University of Paris Diderot,
Hoptial de la Piti Salptrire, Paris, France
Anthony J. Smith, PhD Department of Oral Biology,
School of Dentistry, University of Birmingham, Birmingham, UK
Arthur Veis, PhD Department of Cell and Molecular Biology,
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
 Part I
Pulp Biology