As cementum is one of the hard tissues of the Periodontium which is now being challenging structure to the researcher's, Effort is put forth in understanding the molecular and cellular level of the Cementum. The information is collected from one of the articles from Perio 2000 and also from the slide share forum. This powerpoint gives you the gist and hopefully a better understanding for the learners.

1. Cellular and Molecular
Biology of Cementum
Dr. K. Satya
Dr. Vaishnavi Sanglikar
1st
yearMDS
Dept of Periodontology
Maratha Mandal NGH
institute of Dental
sciences

2. Cementum is the calcified, avascular mesenchymal tissue that forms the outer covering of the
anatomic root. It furnishes a medium for the attachment of collagen fibers that bind the tooth
to surrounding structures (Sharpey’s fibers).

3. Contents
• Introduction
• Regulators of cementogenesis
• Factor-mediated cell activities
Receptor tyrosine kinases
G protein coupled receptors
Serine – threonine receptor kinases
Integrins

4. Periodontium
INTRODUCTION
PROTECT
THE PULP
ANCHORAGE

6. • Cells responsible for cementum formation:
• Cementoblasts: Primary source
Location : close apposition to cementum surface
Strongly resemble osteoblasts
• Cementocytes:
Location : within the mineralized matrix of cementum
Have a slightly lower level of matrix synthesis.
• Fibroblasts within the PDL:
Role is unclear

7. Classification of Cementum:
Based on cellular and fiber content
• Acellular Afibrillar cementum (AAC)
• Acellular Extrinsic Fiber cementum (AEFC)
• Cellular Intrinsic Fiber cementum (CIFC)
• Acellular Intrinsic Fiber Cementum (AIFC)
• Cellular Mixed Stratified Cementum (CMSC)
: Schroeder 1992 :

8. Regulators of Cementogenesis :
Overview : events, cells and factors associated with
cementum.
• Many events required for formation of cementum are well
established, the actual cells and factors required to form
this tissue during development as well as during
regeneration have yet to be defined.

9. • Ability of ideal agents
To promote migration and
attachment of appropriate cells to
the healing site with subsequent
orchestration of cells to allow for
cell differentiation.
To promote mineralization (new
cementum) along
the root surface, with insertion of
periodontal ligament
into cementum and opposing
alveolar bone to
form the periodontium.
EVENTS

11. • PDL fibroblasts:
Responsible for ensuring a functional
PDL region.
• Osteoblasts & associated progenitor cells:
Responsible for preserving the
surrounding alveolar bone.
Histological examination of the healthy periodontium indicates that several
types of mesenchymal cells are important for maintenance of a healthy
periodontium.

12. • Cementoblasts & root surface lining cells:
appear to be limited in function in health but
may be activated during wound healing.
• Paravascular/marrow cells:
Provide the required local nutrients
at the site.

14. Some of the factors that may trigger differentiation of follicle cells or
possibly transformation of Hertwig’s epithelial root sheath cells so as to
function as cementoblasts will be discussed

15. • Accumulating evidence exists to a support a role for
periodontal ligament fibroblasts as inhibitors of
mineralization.
• Thus, there may be distinct cell populations within the
periodontal ligament region that can both promote and
inhibit mineral tissue formation depending upon trigger
factors.
• Also, it is high likely that other sources of cementoblast
or osteoblast progenitor cells include marrow stroma
and paravascular and endosteal fibroblasts.

16. • Many factors have been implicated a role in controlling
several cell activities.
• These factors are known to be associated with
cementum either during development and/or maturation
and/or regeneration.

17. Molecular factors associated with cementum. Included factors (still under investigation) are
important for development/maintenance/regeneration of cementum.
Modified and updated from MacNeil et al.

18. Adhesion and chemotactic factors:
LIGAND
FIBRONECTINFIBRONECTIN
In addition to its role in tissue development, it also purported
to have a notable role in attracting and maintaining
appropriate cells at healing sites.

19. DevelopmentDevelopment
Adhesion molecules
• Osteopontin
• Bone sialoprotein
Mature tooth
Bone sialoprotein: remain localized to the root
surface.
Osteopontin : within the PDL region.
• Laminin: on dentin surface at initiation of
cementum formation speculated to serve a
role in attracting appropriate cementoblasts
like cells to the root surface.
cementoblasts
Early stage of tooth root
development

20.  Further known factors, as well as yet to be identified
novel factors, secreted by epithelial cells may promote
migration and/or adhesion of appropriate cells to the root
surface.
Rationale behind the use of enamel matrix derivative is
that enamel matrix proteins may promote cementoblast
activity including proliferation, migration/adhesion, as
well as cell differentiation.

21. • Bone Sialoprotein
Act as an adhesion molecule to maintain applicable cells at
the root surface
As an initiator of mineral formation along the root surface
Importantly, the temporal and spatial expression of bone
sialoprotein during cementogenesis and bone formation is
consistent with a role for this molecule in promoting
mineral formation.

22. • Osteopontin:
This phosphoglycoprotein contains the well
recognized adhesion domain, arginine-glycine-
aspartic acid (RGD) targeted to specific integrin
receptors, as well as other adhesion regions that act
to promote migration and cell adhesion

24. • Regeneration
• BSP and Osteopontin are expressed by cells linked to
formation of mineralized tissues, while osteopontin also
is expressed by cells within the newly forming
periodontal ligament.

25. • Maturation
Mature cementum contains the adhesion molecules
mentioned above as well as vitronectin and cementum
attachment protein.
• The actual specificity of cementum attachment protein to
cementum, or in fact whether this is a unique protein,
awaits further research and availability of DNA probes to
determine cells expressing cementum attachment protein
during tooth root development and maturation.
• Proteoglycans

26. Mitogens
Mapped during tooth root development include the
members of the transforming growth factor-ß
superfamily, growth hormone, insulin-like growth
factor-I/II and parathyroid hormone–related protein.
• In fact some transforming growth factor-ßs and
parathyroid hormone–related protein may have a role in
regulating cell differentiation and subsequently
mineralization
• Narayanan et al. - Cementum-derived growth factor

28. Factor - mediated cell activities
Factor A Promotes mineralization
of mature Osteoblasts
PDL fibroblasts or
preosteoblasts
Lack ofappropriate
receptors
Factor B priming
Now express the
receptor required for
responding to factor A

29. Growth factors DNA synthesis Differentiation
cytoskeleton
initiate modulate
alter
•The short half life of Growth factors and their association with ECM
and GF binding protein ensure the local effects.
•The ECM molecules and GF’s exert effects through specific cell
surface receptors and when the receptor is bound it interacts with
cytoplasmic effector molecules to initiate a complex cascade of
intracellular events leading to an alteration in gene function.

32. CONTENTS
• Serine – threonine kinase receptor
• Integrins
• Regenerative therapies and cementogenesis in-vivo.
Therapies based on platelet-derived growth factor and
insulin-like growth factor.
Transforming growth factors –ß family members :
Bone morphogenetic proteins 2.3 ,4 and 7.
• Models to study cementogenesis.
• Conclusion
• References.

33. SERINE - THREONINE RECEPTOR KINASES

34. INTEGRINS
Integrins are transmembrane receptors that facilitate
cell-extracellular matrix adhesion.
They are obligate heterodimers.
They are also called as cell adhesion molecules
( CAD ).

36. ROLE OF INTEGRINS
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• Attachment of the cell to the ECM. i.e. extracellular
matrix.
• Signal transduction from the ECM to the cell.

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Saito and Narayan et al :-
mature cementum+ fibroblasts+ FAK
Future studies directed -
CAD + cementoblast maturation.
Few studies have focused on the role of these
integrins during the tooth development.

38. REGENERATIVE THERAPIES AND
CEMENTOGENESIS in-vivo
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This section focuses on pre-clinical and clinical
progress towards using growth factors for stimulating
periodontal regeneration, with an emphasis on the
cementum regeneration.
Regulators of periodontal tissue regeneration that
stimulate formation of bone , periodontal ligament
and the cementum include many different agents
categorized as follows

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41. THERAPIES BASED ON PLATELET-
DERIVED GROWTH FACTOR AND INSULIN –
LIKE GROWTH FACTOR
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• Some of the studies which used the combination or
without are as follows :
1. Park et al :-
Dog model + PDGF + GTR + Ankylosis.
2.1st
human clinical trial :-
Recombinant Combination therapy + 3 Groups

43. TRANSFORMING GROWTH FACTOR –ß
FAMILY MEMBERS:
BMP 2, 3( OSTEOGENIN ) , 4 & 7 ( OP-1 )
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The bone morphogenetic proteins have been
evaluated extensively in orthopaedic models for their
ability to induce osteogenesis.
BMP-2 is the most thoroughly researched member of
the transforming growth factor –ß superfamily for
the promotion of periodontal and peri-implant bone
regeneration..

44. BONE MORPHOGENETIC PROTEIN – 2,3,4 &
7
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Below are some studies reporting the effects of the
BMP’S :-
1)Sigurdsson et al :-
Recombinant BMP-2 + polymer + ankylosis.
2) Ripamonti et al :-
BMP-4 + topical.

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3) 1st
human study :-
BMP-3 + Demineralized bone allograft + × alone
+ pin-point ankylosis.
4)BMP -7 / OP-1 :-
Animal model + ankylosis.

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47. TRANSFORMING GROWTH
FACTOR-ß
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Below are some studies reporting the effects of the
TGF-ß :-
1) Wikesjo et al :-
TGF-ß + PTFE
2)Cochran et al :-
BMP-2 +TGF-ß + implant

48. MODELS TO STUDY CEMENTOGENESIS
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• Investigations targeted at understanding the cellular
and molecular mechanisms controlling development
and regeneration of periodontal tissues have utilized
both in-vitro and in-vivo models.
Commonly used animals are the :
• Rodents
• Canines
• Felines
• Non-human primates

49. IN –VITRO MODELS
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Light and electron microscopy:- level have provided a detailed analysis
of cementum.
Immunocytochemical and in-situ hybridization :-studies provide
information as to the factors expressed by cells associated with the
periodontium.

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Transgenic / knock-out:- offer another tool to assist in determining the
role of specific molecules in controlling tissue functions.
Cell cultures:- provide an additional tool where advances in cell and
molecular techniques allow for selected manipulation of specific cell types.
In addition, cells isolated in culture can be reintroduced into a specific site
in animals and the activity of the cell type confirmed in vivo.

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• According to Grzesik et al :-
Cell phenotype first + then isolating subcloning human
population.
• In a study :-
Cementoblastoma + cementum attachment proteins.

52. IN –VIVO :- GENETICALLY ENGINEERED
ANIMALS
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The mouse is particularly useful as its genome is very well
characterized, and genes can therefore be manipulated with
relative ease.

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• Studies done by
1) Ibaraki-o’ Connor et al :-
Transgenic mouse + Amelogenin

54. CELLAPPLICATIONS : REGIONAL GENE
THERAPY
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• The application of putative molecules to induce or modulate
periodontal regeneration is an area of intensive interest.
However the short half-lives of these molecules at the
healing site may reduce their effects in vivo. Therefore,
methods that provide stability of exogenous molecules at the
healing site may be advantageous toward maximizing wound
repair.
• Gene transfer can be performed with strategies for either ex
vivo or in vivo transfer of the desired transgene.

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• The most important advance for viruses as gene
transfer vectors was the generation of ‘‘packaging
cells’’ that permit the production of high titers of
replication-defective recombinant virus, free of
wild-type virus; also called gutless viruses.
• The use of gene transfer techniques should enable
one to modulate periodontal regeneration, as well as
assist in enhancing understanding of the
mechanisms involved in wound healing.

58. CONCLUSION
• Despite many years of research and the importance that cementum is thought to
play in the reparative process following periodontal disease, very little is known
about the cells responsible for formation of cementum, cementoblasts. The wealth
of what is known about cementum comes from numerous, detailed studies of its
histology and composition, which has been touched briefly.
• Protein extracts of mature cementum promote cell attachment, migration and
stimulate protein synthesis of gingival fibroblasts and periodontal ligament cells.
Investigation of these extracts revealed the presence of bone sialoprotein,
osteopontin, vitronectin and fibronectin.
• Immunocytochemistry and in situ hybridization confirmed the presence of these
proteins and further identified osteocalcin, g-carboxyglutamic acid, osteonectin,
proteoglycans and several growth factors.
• Two additional molecules, an adhesion molecule and a growth factor, have been
identified and initial data suggest that they may be unique to cementum. Cementum
attachment protein may prove to be a cementum-specific collagenlike molecule,
while a factor initially named cementum-derived growth factor, now considered to
be an insulin-like growth factor-I–like molecule may prove to have properties
similar to those of insulinlike growth factor-I.

59. • This is a dynamic time for researchers and clinicians devoted to
optimizing periodontal/implant regenerative therapies. The
explosion in understanding of regulators of cell function, coupled
with tools that allow researchers to engineer cells so as to express
specific factors, added to improved delivery systems for
controlling release of cells/factors at a given site, now allows
treatment modalities to be designed based on sound scientific data.
• Information gained from these studies should provide the
foundation required for designing more predictable regenerative
therapies when compared with those available at present.

60. REFERENCES
• Textbook : Carranza’s Clinical Periodontology {11th
edition}
• Textbook :Biology of periodontal connective
tissues {P.Mark Bartold, A.Sampath Narayan}
• Nazan E.Saygin , William g, Martha S. Molecular
and cell biology of cementum. 2000: (24), 73-98.