Braz J Oral Sci. January/March 2005 - Vol.

4 - Number 12

Dental cementum reviewed:

development, structure, composition,
regeneration and potential functions
Patricia Furtado Gonçalves 1
Enilson Antonio Sallum 1 Abstract
Antonio Wilson Sallum 1 This article reviews developmental and structural characteristics of
Márcio Zaffalon Casati 1 cementum, a unique avascular mineralized tissue covering the root
surface that forms the interface between root dentin and periodontal
Sérgio de Toledo 1
ligament. Besides describing the types of cementum and
Francisco Humberto Nociti Junior 1
1
Dept. of Prosthodontics and Periodontics,
cementogenesis, attention is given to recent advances in scientific
Division of Periodontics, School of Dentistry understanding of the molecular and cellular aspects of the formation
at Piracicaba - UNICAMP, Piracicaba, São and regeneration of cementum. The understanding of the mechanisms
Paulo, Brazil. involved in the dynamic of this tissue should allow for the
development of new treatment strategies concerning the approach
of the root surface affected by periodontal disease and periodontal
regeneration techniques.

Received for publication: October 01, 2004 Key Words:

Accepted: December 17, 2004 dental cementum, review

Correspondence to:
Francisco H. Nociti Jr.
Av. Limeira 901 - Caixa Postal: 052 -
CEP: 13414-903 - Piracicaba - S.P. - Brazil
Tel: ++ 55 19 34125298
Fax: ++ 55 19 3412 5218
E-mail: nociti@fop.unicamp.br

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Braz J Oral Sci. 4(12): 651-658 Dental cementum reviewed: development, structure, composition, regeneration and potential functions
Introduction
Cementum is an avascular mineralized tissue covering the
entire root surface. Due to its intermediary position, forming
the interface between root dentin and periodontal ligament,
cementum is a component of the tooth itself, but belongs
functionally to the dental attachment apparatus, that is,
the periodontium. One of the main functions of cementum
is to anchor the principal collagen fibers of the periodontal
ligament to the root surface, but it also has important
adaptative and reparative functions, playing a crucial role
to maintain occlusal relationship and to protect the integrity
of the root surface.
Until recently, knowledge of the development and the
general structure of the periodontium was limited to
morphological information, although, during the last
decade, rapid progress has been made in understanding
the molecular and cellular biology of periodontal tissue
development and regeneration, including cementum.
Dental cementum is unique in various aspects: it is
avascular and not innervated, does not undergo continuous
remodelling like bone, but continues to grow in thickness
throughout life1. In contrast with these specific histological
characteristics, it appears not to be specific at the cellular
and molecular level2. Unlike dentine and enamel, where there
are clear differences in the proteins present in these tissues
and the factors regulating their functions when compared
with bone, cementum has not demonstrated to express
specific proteins, appearing to contain factors in common
with bone and to be developmentally controlled by similar
factors 2-3.
There is accumulating histological evidence that cementum
is critical for appropriate maturation of the periodontium,
both during development and as well as that associated
with regeneration of periodontal tissues3. Recent studies
have contributed to an understanding of the possible
involvement of some of the molecular factors in cementum
regeneration 4, but cementogenesis, on a cell biological
basis, continues to be poorly understood. The aim of this
chapter is to give a comprehensive review about some
important aspects of this unique tissue, including its
varieties, development, structure, composition,
regeneration and potential functions.
Types of cementum
Traditionally, cementum has been classified as cellular and
acellular, depending on the presence or absence of
cementocytes in its structure. Another classification
includes intrinsic or extrinsic fiber cementum, depending
on the presence of collagen fibers formed by cementoblasts
or by fibroblasts, respectively 5-6. Mainly three cementum
types differing in these aspects are distinguished in humans.
Acellular afibrillar cementum covers minor areas of the
enamel, particularly at and along the cementoenamel
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junction (Figure 1). The areas and location of acellular
afibrillar cementum vary from tooth to tooth and along the
cementoenamel junction of the same tooth 6-9. Its major
structural organic components are glycosaminoglycans 6,
and its functional significance is unknown. The lack of
collagen fibrils indicates that this cementum variety has no
function in tooth attachment.
Fig. 1. Acellular cementum (arrow). Notice that acellular afibrillar
cementum overlaps the cervical end of the enamel. This is the most
common relationship between the two tissues. Unstained, 100x
Cellular intrinsic fiber cementum contains cementocytes
embedded in a collagenous matrix of intrinsic collagen
fibers (Figures 3 and 4). These collagen fibers are oriented
mostly parallel to the root surface and course in a circular
fashion around the root6. A fast matrix deposition by the
cementoblasts, which occurs in the space between
deviating epithelial cells of Hertwig´s root sheath and the
dentinal surface appears to be the reason for the
incorporation of some of the cementoblasts 10-11. Cellular
intrinsic fiber cementum is found in the furcation, on the
apical root portion, in old resorption lacunae and in root
fracture sites, playing an important role as an adaptative
tissue that brings and maintains the tooth in its proper
position and also participating in the repair process,
although it has no immediate function in tooth
attachment1,6 . Only cellular intrinsic fiber cementum can
repair a resorptive defect of the root in a reasonable time,
due to its capacity to grow much faster than any other
type of cementum10.
Acellular extrinsic fiber cementum is mainly found on
cervical and middle root portions, covering 40% to 70% of
the root surface. On anterior teeth, it may also cover part of
the apical root portion, since its apical extension increases
from posterior to anterior teeth. It serves the exclusive
function of anchoring the root to periodontal ligament. The
acellular extrinsic fiber cementum matrix consists of a dense
fringe of short collagenous fibers that are implanted into
the dentinal matrix (glycosaminoglycans) and are oriented
Braz J Oral Sci. 4(12): 651-658 Dental cementum reviewed: development, structure, composition, regeneration and potential functions
about perpendicularly to the root surface 6 . When they
become elongated and eventually continuous with the
principal periodontal ligament fibers they are called
Sharpey´s fibers. Although acellular extrinsic fiber
cementum is a quite constantly growing tissue,
appositional lines (Figure 2) represent the periodical
deposition of cementum layers in frequent association
with an abrupt change in the direction of Sharpey´s fibers12.
Moreover, as can be deducted from faster growth rates
on distal (4.3mm/year) than on mesial (1.4mm/year) root
surfaces 13 , acellular extrinsic fiber cementum has the
potential to adapt to functional alterations such as mesial
tooth drift. In humans, the extrinsic fibers traverse and
intermingles the intrinsic fiber cementum variety either
sporadically or densely arrayed in parallel; this mixed
cementum is referred to as cellular mixed stratified
cementum 6.
Fig. 2: Acellular cementum. At a higher magnification, notice
that this type of cementum has incremental lines of growth (arrow)
which are oriented parallel to the root surface. Tomes’ granular
layer (*)and dentinal tubules (thin arrow) are also visible in the
field.
Fig. 3a: Cellular cementum (arrow). It is characterized by the
presence of lacunae with canaliculi in which reside cementocytes.
However, the cells are absent in ground section preparations.
Unstained, 40x
Fig. 3b: Higher magnification of previous image. Notice that the
canaliculi of cementocytes (*) have a tendency to be polarized and extend
toward the periodontal ligament side of the root. Unstained, 400x
Origin and development of cementum
Based on the observation that populations of cementoblasts
are phenotipically distinct, some authors defended the
possibility that acellular and cellular cementum have
different developmental origin 14 . Some studies 15-16
suggested that cementoprogenitor cells arise from the
dental follicle proper, which is of ectomesenchymal origin
(that is, a derivative of the cranial neural crest). However,
as pointed out by Thomas & Kollar17, labeled cementoblasts
could also be of epithelial origin, since cells of the enamel
organ, which give rise to HERS, also incorporate 3H-
thimidine prior to transplantation in mice. More recent
ultrastructural and immunohistochemical studies support,
indeed, the hypothesis that cementoblasts originate from
epithelial cells of HERS when they undergo an epithelial-
mesenchymal transformation 18-20 . There is increasing
evidence that Hertwig’s epithelial root sheath is actively
involved in the formation of both acellular and cellular
cementum.
Diekwisch21 (2001), published an extensive literature review
on early cementogenesis and performed a detailed
morphological and molecular analysis to illustrate and verify
key issues in the current debate about epithelial and
mesenchymal contributions to root cementum. The author
demonstrated that prior to cementogenesis, Hertwig’s
epithelial root sheath disintegrates and dental follicle cells
penetrate the epithelial layer to invade the root surface.
Other studies confirmed that HERS became disrupted or
disintegrated prior to cementum deposition, and visualized
how mesenchymal cells from the dental follicle penetrated
the HERS bilayer and deposited initial cementum, while
immediately adjacent epithelial cells were separated from
the root surface by a basal lamina and did not secrete any
cementum22-23. Human specimen from the Gottlieb collection
indicated that HERS was removed from the root surface
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Braz J Oral Sci. 4(12): 651-658 Dental cementum reviewed: development, structure, composition, regeneration and potential functions
prior to cementum deposition. In situ hybridization and
immunolocalization data revealed that both amelogenin
mRNAs and enamel proteins were restricted to the crown
enamel and were absent from the root surface and from the
cervical-most ameloblasts adjacent to the root margin24-26.
On Western blots, cementum protein extracts did not cross-
react with amelogenin antibodies 25 . These studies in
conjunction with a literature review together confirmed the
theory of cementum as a dental follicle derived connective
tissue that forms subsequent to HERS disintegration.
Briefly, cementogenesis begins with the deposition of a
matrix on the dentin surface by Hertwig’s epithelial root
sheath, disruption of the HERS, migration and organization
by ectomesenchymal cells from the dental papilla, and their
subsequent differentiation into cementoblasts 25,27 . The
matrix they produce surrounds cells producing cementum,
the cementoblasts, and the cementoblasts are generated
by differentiation of progenitor cells, which in turn are
believed to arise from the dental follicle.
The fate of HERS following the onset of cementogenesis is
also controversial. Traditional thinking proposed that HERS
disintegrated into small clusters and/or strands of epithelial
cells that survived indefinitely in the periodontal ligament.
More recent studies have suggested that epithelial cells of
the Hertwig’s root sheath undergo epithelial /mesenchymal
transformation into fibroblasts and cementoblasts, that
deposit acellular and cellular cementum, respectively1,28. The
possibility that some epithelial cells of the root sheath
undergo epithelial/mesenchymal transformation and
subsequently secrete cementum matrix must be investigated
further. There is evidence that cells of the inner layer of the
root sheath become incorporated in cellular cementum or
trapped between cementum and dentin during formation of
the apical part of the root29. The only incontrovertible fact
is that many cells of the HERS retain an epithelial phenotype,
and survive in periodontal ligament as the epithelial rests
of Malassez1,6.
Composition
Since cementum is not a uniform, mineralized connective
tissue, differences in the proportional composition of the
chemical constituents exist between the cementum varieties.
Thus, the percentages of its chemical components may vary
from sample to sample, particularly in different species.
Biochemical studies have shown that cementum has a similar
composition to bone. To about equal parts per volume,
cementum is composed of water, organic matrix and mineral.
About 50% of the dry mass is inorganic, and consists of
hydroxyapatite crystals. The remaining organic matrix
contains largely collagens, glycoproteins and proteoglycans1.
Mineral composition
Cementum is generally less mineralized than root dentin
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from the same teeth30-31, although not without exception32.
Acellular extrinsic fiber cementum appears more highly
mineralized than cellular intrinsic fiber cementum and
cellular mixed stratified cementum33, what can in part be
explained by the presence of uncalcified spaces, such as
lacunae and by the uncalcified core of Sharpey’s fibers.
Chemical analysis and physicochemical studies indicate
that the mineral component is the same as in other calcified
tissues; that is, hydroxyapatite (Ca10(PO4)6(OH)2), with small
amounts of amorphous calcium phosphates present34. Due
to its lower crystallinity of the mineral component
(compared to other hard tissues), cementum has a greater
capacity for adsorption of fluoride and other elements over
time but also more readily decalcifies in the presence of
acidic conditions 1.
As in other hard tissues, the hydroxyapatite of cementum
is not pure, but contains other elements (ions) incorporated
into mineral phase during mineralization, depending on their
concentration in the fluid environment. Over time, the
concentration may change by additional uptake or
substitution by other ions. Thus, cementum contains 0.5-
0.9% magnesium35-36, about half that in dentin, and it is
lower at the surface than in deeper layers of cementum.
The significance of the low Mg +2 content in cementum
remains obscure, but agrees with the notion that the
composition of cementum is more similar to bone tissue
than to dentin. In contrast, the distribution of fluoride shows
the opposite trend. Cementum have a high fluoride content
compared to other mineralized tissues (up to 0.9% ash
weight), and this concentration shows a general increase
with age and vary with fluoride supply to the individual, as
it is in bone, dentin and enamel as well37. Cementum also
contains 0.1-0.3% sulfur as a constituent of the organic
matrix38, and a number of trace elements may be present in
concentrations detectable by electron microprobe analysis,
in particular Cu +2 , Zn +2 and Na +2 36 ; however, their
distribution and significance do not seem to have been
studied in detail.
Organic composition
The organic matrix of cementum is composed primarily of
collagens. Type I collagen plays structural as well as
morphogenic roles and provides scaffolding for mineral
crystals; it is the major component, accounting for 90% of
all collagens. The type III collagen, which coats type I
collagen fibrils, accounts for only 5%3.
Cementum contains two major non-collagenous proteins,
bone sialoprotein (BSP) and osteopontin (OPN). Both are
phosphorilated and sulfated glycoproteins. These proteins,
which are prominently expressed in acellular extrinsic fiber
cementum and acellular afibrillar cementum, bind tightly to
the collagenous matrices and hydroxiapatite, and they
possess cell attachment properties through the Arg-Gly-Asp
Braz J Oral Sci. 4(12): 651-658 Dental cementum reviewed: development, structure, composition, regeneration and potential functions
(RGD) sequence, that binds to integrins39-40. Both proteins
are expressed during early tooth root development by cells
along the root surface. Root surface cells express the BSP,
and it is also present in mature teeth. In contrast, OPN is
present within the periodontal ligament region of the mature
teeth. These two proteins are believed to play a major role in
the differentiation of the cementoblasts progenitor cells to
cementoblasts 3. The BSP is believed to have adhesion
function to root surface cells and to participate in initiating
mineralization. It is chemotatic to pre-cementoblasts and
promotes their adhesion and differentiation41. Many cells
express the OPN during periods of cementogenic activity. It
regulates cell migration, differentiation, and survival through
the interaction with integrins, and also participates in
inflammation by regulating monocyte-macrophage activation,
phagocytosis, and nitric oxide production. In teeth and
cementum, it may regulate biomineralization by at least two
mechanisms: regulating bone cell differentiation and matrix
mineralization42.
Fibronectin 43 , which is believed to bind cells to the
extracellular matrix, and tenascin are present in HERS during
odontoblast differentiation, and later at the attachment site
of periodontal ligament to the root surface. Osteonectin,
osteocalcin and laminin are other matrix components found
in cementum. Osteonectin is expressed by cementoblasts
producing cellular extrinsic fiber cementum and cellular
intrinsic fiber cementum 44 . Osteocalcin appears to be
involved in the mineralization process45. The proteoglycans,
small proteins that are widely distributed in mammalian
species, are also present in cementum46. Biochemical analysis
of extracts of human cementum have identified chondroitin
sulfate, dermatan sulfate and hyaluronic acid47.
The enzyme alkaline phosphatase is believed to participate
in cementum mineralization. In rat molars, the enzyme is
heterogeneously distributed in the periodontal ligament,
with the highest activity being found adjacent to alveolar
bone and cementum. The enzyme activity adjacent to cellular
intrinsic fiber cementum is higher than that to acellular
extrinsic fiber cementum, and the thickness of the later
correlates positively with the enzyme activity48.
Several polypeptide growth factors with ability to promote
proliferation and differentiation of putative cementoblasts
are found in cementum matrix. These include BMP-2, -3
and –4, PDGF, α-and β-FGFs, TGFβ, PTH and IGF-13-4,49.
While these molecules have been called growth factors,
their role during tooth development does not appear to be
related to proliferative activity. In fact, some TGFbs and
PTH-related protein may have a role in regulating cell
differentiation and subsequently mineralization49-50.
It is important to know that many of these components are
also present in bone; however, molecules unique to
cementum have also been described. One of these is an
IGF-1 isoform, referred to as cementum growth factor (CGF),
now considered to be an insulin-like growth factor1-like
molecule, with similar properties to those of IGF-1, but
larger than IGF-1 in molecular size51. The second molecule
is a collagenous protein referred to as cementum attachment
protein (CAP). Antibodies to CAP immunostain only
cementum and not other periodontal components or other
tissues52. In bovine tooth germs, the CAP is expressed by
cementoblasts, and in cementum its expression pattern is
different from that of type I collagen53. CAP promotes the
adhesion and spreading of mesenchymal cells; however, it
promotes the adhesion of mineralized-tissue-forming cells,
preferentially 54-55.
Cementum and Periodontal Regeneration
Although the extent of injury and the amount of lost tissue
that must be filled are important determinants, whether a
damaged tissue heals by regeneration or repair depends
on two crucial factors: the availability of needed cell types
and the presence or absence of the cues, and signals
necessary to recruit and stimulate these cells.
One major goal of regenerative periodontal therapy is new
cementum formation and restoration of soft tissue
attachment to the cementum. This process requires
cementoblasts, and the origin of cementoblasts and the
molecular factors regulating their recruitment and
differentiation are not fully understood. In vivo animal
models to evaluate cementogenesis during tooth
development, the expression pattern of specific matrix
molecules, and in vitro studies about the effects of
cementum components on periodontal cells have provided
important knowledge on how cementum components can
regulate cementum regeneration3, 56-59. Although cementum
formation in rodents differs from that in humans 18, the
observation of Liu et al (1997)60 indicates that periodontal
ligament may be one source of cementoblasts progenitor
cells in adult humans. These investigators demonstrated
that a small proportion of clones of cells cultured from
human periodontal ligament form cementum-like mineralized
nodules in culture, and also produce cementum-specific
markers61. Cementoblasts may also be derived from stem
cells present in the periodontal ligament, gingiva, and
alveolar bone, when the pool of available progenitors is
likely to be reduced or absent; however, the molecules
responsible for recruiting and differentiating these cells
and the mechanisms involved remain to be better
investigated 3 .
A variety of chemotatic factors, adhesion molecules, growth
factors, and matrix constituents participate together in the
recruitment of cementoblasts progenitors, their expansion
and differentiation. For example, cementum contains
molecules that promote chemotatic migration, adhesion,
proliferation and differentiation of some periodontal cells
types better than others, and these molecules are not
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Braz J Oral Sci. 4(12): 651-658 Dental cementum reviewed: development, structure, composition, regeneration and potential functions
detectable in other periodontal structures 51-52,55,61-63 .
Adhesion molecules that cause negative selection by
excluding unwanted cells are also present in cementum54.
Thus, the cementum microenvironment contains all the
components necessary for cell recruitment, proliferation and
differentiation, and molecules from the circulation are not
necessary 44 .
All these observations underscore the importance of
restoring or providing the cementum microenvironment to
initiate and promote new cementum formation. The integrity
of cementum is altered by periodontal disease due to
deposition of bacterial endotoxins 64 , and diseased
cementum is removed during periodontal therapy65. Dentin
not covered by cementum undergoes resorption. Root
conditioning does not restore the original composition of
cementum local environment, and instead expose molecules,
especially type-I collagen, which has poor cell specificity65.
The application of some growth factors is not likely to
provide the complete repertoire of the needed molecules,
since the concentration and type of growth factor on
cementum change continuously during the healing
process66. Similarly, while barrier membranes can facilitate
population of the site by needed cells, they are not likely to
provide the local environment for their differentiation67 .
Further, providing enamel proteins 68, while likely to be
conductive to early cementogenesis, may not provide
appropriate environment for recruiting cementoblasts
progenitors in adults and for their differentiation. Indeed,
extracellular matrix components are expressed during
periodontal healing67,69; however, whether all molecules are
expressed in adequate temporal sequence is not known.
All these factors together may explain why cementum
regeneration is not always predictable for the available
regenerative procedures.
Recent in vivo studies using rat periodontal defect models,
have shown that both BSP and OPN are expressed by cells
linked to formation of mineralized tissues, while
osteopontin is also expressed by cells within the newly
formed periodontal ligament69. Future research directed at
overexpressing or blocking expression of these molecules
during periodontal wound healing should provide additional
information required to establish the real function of these
molecules in mineralized tissues and also determine the
value of using such agents clinically for enhancing
regeneration of periodontal tissues3.
Future directions on Cementum research
The development of the cementum research in the cellular
and molecular fields is promising, since several laboratories
have reported successful isolation and propagation of cells
(from both animal and human sources) exhibiting an
apparent cementoblastic phenotype in vitro70-72. These cells
have been shown, reproducibly, to form histologically
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proven cementum-like tissue following in vivo
transplantation into immunodeficient mice44,72.
One of the most important benefits of the establisment of
such combined in vitro/in vivo models is that they will allow
for elucidations of the relationship between osteoblasts
and cementoblasts, besides providing more information
regarding the specific mechanisms involved in maintenance
of cementum structure and function in humans on the
cellular and molecular level. Similarly, the in vitro/in vivo
system can also be used for further elucidation of the modes
of action of current available regenerative products, such
as Emdogain, with apparent cementum-growth-promoting
activities.
This knowledge probably will allow for the development of
strategies for regenerating cementum with cell-based
therapies, by means of recruiting cells with cementoblastic
potential, inducing their differentiation and excluding
unwanted osteoblastic precursors. Furthermore, the use of
these models allows for direct in vivo human
experimentation, which may be particularly important,
because cementum has been reported to differ between
species in some aspects of its physiology9-11. In principle,
cementogenic cells can be isolated from a relatively small
specimen, expanded in culture, and subsequently
transplanted to the same patient. Primary human
cementoblasts can be efficiently grown from dissected
fragments of healthy root cementum treated with
colagenase: the culture conditions are fairly standard and
it is possible to obtain large numbers (in the range of 108-
109) of committed cementogenic cells from a single tooth44,72.
However, a significant drawback of this model is the
requirement that healthy teeth be extracted for the cultures
to be established, since it is still not clear whether
cementogenic cells can be obtained, by this approach, of
aged and/or diseased patients. These drawbacks will
probably lead, in near future, to the investigation of sources
other than cementum for cell isolation (i.e.: periodontal
ligament, gingiva, bone marrow).
Once the cementogenic cells are selected and the molecules
critical for cementum regeneration are identified, the next
step may be to develop an efficient and relatively simple
delivery system to be used for periodontal regeneration.
This probably may be one of the major problems, since
cementum is a mineralized “interface” tissue, connecting
mineralized dentin and non-mineralized fibrous periodontal
ligament – what implies that a successful delivery system
should somehow reconcile these two distinct environments.
In this concern, molecules such as CAP show some
promise 60-62, due to its mineral-binding domain. Several
integrins as well as their natural ligands (e.g. collagens,
BSP, OPN) are known to be expressed by cementoblastic
cells67, implying that they may be important regulators of
cementogenesis. This also indicates that targeting integrin
Braz J Oral Sci. 4(12): 651-658 Dental cementum reviewed: development, structure, composition, regeneration and potential functions
receptors may be beneficial for stimulating cementum
regeneration.
In summary, there is still much to study about cementum
tissue regeneration via cell- and matrix-based therapies,
but, without any doubt, recent developments in basic
science indicate that these approaches are feasible and
worth exploring.
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