Warning: include_once(../article_type.php): failed to open stream: No such file or directory in /home/suxhorbncfos/public_html/oajggm/OAJGGM.MS.ID.555635.php on line 112
Warning: include_once(): Failed opening '../article_type.php' for inclusion (include_path='.:/opt/alt/php56/usr/share/pear:/opt/alt/php56/usr/share/php') in /home/suxhorbncfos/public_html/oajggm/OAJGGM.MS.ID.555635.php on line 112
INSERM UMR-S1124, University Paris Cité, Faculté des Sciences Fondamentales et Biomédicales, Cellules souches, Signalisation et Prions, Paris, France
Submission: May 05, 2018; Published: May 18, 2018
*Corresponding author:Goldberg Michel, Cellules souches, Signalisation et Prions, INSERM UMR-S1124, University Paris Cité / Faculté des Sciences Fondamentales et Biomédicales, 45 rue des Saints Pères, Paris 6, 75006, France.
How to cite this article: Michel G. What Ages First: Pulp or Dentin?. OAJ Gerontol & Geriatric Med. 2018; 4(2): 555635.
Dental pulps stem cells have regeneration potentials. Young pulp cells convert when they mature into cell-producing dentin. In the pulp, the targeted cells are specifically pulpoblasts, fibroblasts, immune and inflammatory cells. In the coronal part of the teeth, capillaries irrigate 100-150 m round or oval domains, allowing the cleaning of continuous zones. In the root, an uninterrupted fish net-like arrangement is located at the periphery of the dental pulp. Thrombus leads to degenerative processes, or to pulp degradation. Pulp necrosis, apoptosis, or nemosis guide pulp impairment. They may influence pulp renewal. Stem cells include Dental Pulp Stem Cells (DPSCs), Exfoliated Deciduous Teeth Stem Cells (SHEDs), Platelet Derived Growth Factors (PDLSCs), Dental Follicle Precursors (DFSCs) and Apical Papilla Stem Cells (SCAPs). An ascending layer of cells issued from the apical papilla mesenchyme contributes to pulp regeneration. Initially, apical cell-rich zones are undifferentiated, and cell sliding involves the transfer from the apical part of the root to the crown, moving from the sub-odontoblastic layer to the radicular dental pulp. Linked by intercellular junctional complexes, pulp cells are interconnected by gap- and tight- junctions. They are transported toward the crown, tightly associated by intercellular junctions. In addition, lateral sliding occurs between the mesial cavities and the central pulp. Later, translocation takes place between the central pulp and the distal horn. This is obvious after an injection with Bio (a Glycogen Synthase Kinase-3 specific inhibitor implicated in regenerative medicine). After a single injection, labeled cells become scarce and in the apical papilla mesenchyme, cells slide laterally from the mesial to the distal pulp horn, where they become undetectable. As pulp cells become older, VEGF promotes blood vessel formation. The activation of the ERK pathway leads to the expression of osteogenesis-related genes, such as Cbfa1, Col I, ALP, and OCN, responsible for dentin formation and mineralization of extracellular matrix components (Tables 1 & 2). TNF-α, Notch, p38 MAPK, TGF-β, Msx1, Msx2, and JNK signaling pathways are implicated in osteogenic differentiation. Dental pulp cells, young and/or old odontoblasts/osteoblasts contribute to bone and dental tissues regeneration. Adipose tissue is another source of mesenchyme stem cells. Young pulp cells become older, producing a dentin layer that contribute efficently to geriatric odontology.
Keywords: Pulp; Dentin; Stem Cells; A Mini-Review.
Deep carious lesions lead to irreversible pulp damage. Stem
cells located in dental pulps replicate and retain potentials
for regeneration [1-12]. They are implicated in the repair of
defective cell types, carious lesions and genetic therapies. After
the formation of a thin outer mantle dentin, a thick circumpulpal
dentin is created, including the primary and secondary dentins
orthodentin (tubular dentin) and osteodentin, which are
developed long after the pulp formation. Reparative (or
tertiary) dentin is formed after a pulp horn exposure (Figure 1).
In the pulp, the targeted cells are specifically pulpoblasts,
fibroblasts, immune and inflammatory cells. Different groups
of cells are concerned by pulp regeneration. They include
odontoblast-like cells, a whole collection of immune cells, central
and peripheral nerves, ending at close vicinity of odontoblast cell
bodies. Odontoblasts involve the Raschkow’s sub-odontoblastic
network. Vascular and lymphatic vessels recolonize and irrigate
the wounded pulp tissue [13,14]. Altogether, these cells play a
role in pulp physiology, including functionality within the central
pulp (Figure 2).
In the coronal part of the teeth, capillaries irrigate 100-150
m broad domains, round or oval areas, allowing the cleaning
of continuous adjacent zones [15,16]. Along the periphery of
the pulp, capillaries allow peripheral vascularization and this
distribution favours pulp regeneration. In the middle of the
pulp, arterioles and venules are in continuity and contribute
to stimulate pulp regeneration. In the root part, a fish net–like
arrangement is continuous at the periphery of the dental pulp.
Thrombus leads to degenerative processes, and ultimately to
pulp degradation. Pulp necrosis, apoptosis, or nemosis leads
either to the totality of pulp degradation, or specifically allows
pulp renewal [17,18] (Figure 3).
In contrast, the formation of dentin implicates a series
of molecules (Table 2). Mineralizing molecules are including
adiponectin, type I collagen, alkaline phosphatase, DMP-
1, 1-dentin sialoprotein, dentin sialoprotein and dentin
sialophosphoprotein, MEPE, dentin matrix metalloprotease
MMP-3, MMP-9, PGs (decorine, biglycan, osteoadherin,
fibromodulin) and osteopontin [19-22]. To conclude with the
construction of dental tissues, first a dental pulp is formed, and
later a dentin layer is deposited along the initial layer of mantle
dentin (orthodentin and osteodentin). At the periphery of the
pulp, odontoblasts polarize and differentiate (Figure 4).
The prevalence of caries is rather high (about 85% in the
65-74 year-old patient) and significant in the aging population.
In younger patients, the 35-45 year-old group of patients, the
carious prevalence is limited to 80.2%. Pulp inflammation is
lower in young patients and higher in the older patient group.
In this clinical context, a significant impact is related to the aging
Pulp stem cells constitute a heterogeneous population.
In dental tissues, stem cells include 1) dental pulp stem cells
(DPSCs), 2) exfoliated deciduous teeth stem cells (SHEDs),
3) platelet derived growth factor (PDLSCs), 4) dental follicle
precursors stem cells (DFSCs) and 5) apical papilla stem cells
(SCAPs). Adipose-Derived Stromal/Stem Cells (ASCs) play
crucial role in the treatment of craniomaxillofacial defects
. ASCs are committed toward an osteogenic phenotype.
Angiogenesis and osteogenesis support bone regeneration.
Plasma membrane-derived vesicles are important mediators
in cell-to-cell communication. Growth factors, cytokines,
RNAs and microRNA perform biological activities on target
cells. They activate regenerative or reparative processes .
Bioengineering teeth may be obtained from cultured tooth bud
cells [24,25] (Figures 5 & 6).
ASCs derived from pulp donors showed a high expression
of osteogenic markers. This is the case for Osteopontin (OPN),
Osteocalcin (OCL), and BMP-2. A high mineral content is found in
the pulp and dentin of old patients [1,9,21,26] (Figure 7).
Pulp regeneration implies a cascade of cells, sliding from
the apex toward the upper part of the crown. In the apical
part, undifferentiated cells contribute to colonize the root. The
ascending cells move beneath the odontoblast layer, and form a
continuous layer that will further colonize the sub-odontoblastic
layer. They proliferate, multiply and concentrate in the apical
cell-rich zone. In the root, cell sliding starts near the apical part.
The ascending layers of cells contribute to pulp regeneration
[24,25] (Figure 8).
Initially, pulp cells are undifferentiated, and move from the
sub-odontoblastic layer to the collar of the tooth. Presumably,
cell sliding involves an ascending transfer from the apical part of
the root toward the crown [27,28].
Connected by intercellular junctional complexes, namely
desmosome-like junctions, pulp cells are linked by gap- and tightjunctions
and they move simultaneously. They are transported
along an ascending way, tightly connected by intercellular
junctions. They move from the central part of the root to the
periphery of the crown where they fan out [29-32] (Figure 9).
In addition, lateral sliding is occurring between mesial
cavities prepared after drilling, and the central pulp horn.
Afterward, translocation occurs between the central horn and
the distal pulp. This is noticeable mostly for rats injected with
Bio (a Glycogen Synthase Kinase-3 specific inhibitor implicated
in regenerative medicine ). After a single injection, labeled
cells become scarce in the mesial part of the pulp and they
are grouped in the central pulp area. Bio-labeled cells located
beneath the odontoblast layer are less numerous in the distal
pulp. It comes out that cells slide laterally from the mesial pulp
to the distal pulp horn whereas sliding becomes undetectable in
the distal part of the pulp.
The conclusions that arise from these experimental
approaches are 1) that cells slide in an ascending way from
the apex toward the crown, 2) afterward, lateral sliding
occurs between the mesial horn and the central/distal pulp.
This evolution takes place mostly in the coronal pulp, leading
to the terminal differentiation of odontoblasts. In addition,
terminal differentiation was strongly linked to the strategic
mesenchymal stem cells that are implicated in dentinogenesis,
and angiogenesis. Pulp cells are implicated in the implantation
of bioactive molecules located in the root, within the dental pulp
Pulp cells are implicated in geriatric odontology.
Angiogenesis shows vascular endothelial growth factor, as well
as platelet-derived growth factor, and hepatocyte growth factor.
IGF-1, VEGF-D and interleukine-8 improve the recruitment of
undifferentiated and/or hematopoietic stem cells associated to
different tooth compartments . Combined with biomaterials,
such as -tricalcium phosphate, bioactive glass and plateletrich
plasma, the dental pulp or bone tissue display potential in
pulp regeneration. Pulp renewal is also dependent of adiposederived
stromal /stem cells (ASCs).
As cells become older, VEGF promotes new blood vessel
formation, and they are also able to recruit hematopoietic
stem cells. The activation of the ERK pathway in ASCs leads to
the expression of osteogenesis-related genes, such as Cbfa1,
Col I, ALP, and OCN, which appears to be responsible for pulp
mineralization of Extracellular Matrix Components (ECM)
As a conclusion, TNF-α may enhance the osteogenic
differentiation of ASCs by increasing specific gene expression,
such as osteopontin (OPN), runx-related transcription factor
2 (RUNX-2), and Alkaline Phosphatases (ALP) (Tables 1 & 2)
. Molecular investigations clearly confirmed that ERK,
TNF-α, Notch, p38 MAPK, TGF-β, Msx1, Msx2, and JNK signaling
pathways are strongly implicated in the odontogenic/osteogenic
differentiation of ASCs [31-36].
Altogether, young and old dental pulp cells, young and old
odontoblasts and osteoblasts contribute to bone and dental
tissues differentiation/regeneration. Adipose tissue is an active source of mesenchyme stem cells. Noticeably, aging tissues
contribute efficiently to geriatric odontology.