Volume 85 Number 10
AAP Centennial Commentary
The Evolution of Periodontology: Science Always Wins
Robert J. Genco*
I
n celebration of the American Academy of Peri-
odontologys 100th anniversary, I have been asked
to give a perspective on the importance of the role
of science in the evolution of periodontology.
Current tenets of periodontology are largely based
on research, mainly published in peer-reviewed arti-
cles such as the 150+ papers assembled by Kornman,
Robertson, and Williams.1 Often the initial ideas come
from case reports, but the strong evidence which is
needed to guide clinical practice frequently comes
from well-designed and well-executed randomized
controlled clinical trials and basic science studies
that are replicated and published. The main tenets of
our current understanding of periodontal disease and
its management can be summarized as six pillars of
knowledge based on the past published literature.1
They are:
I. Periodontitis is a common disease of man that
affects almost half of adults in the United States.2
II. Bacteria play a critical role in the etiopathogen-
esis of gingivitis and periodontitis.
III. Periodontitis is characterized in large part by
chronic immunopathologic responses to periodontal
organisms, which lead to destruction of connective
tissues and bone that surround and support the teeth.
IV. Periodontal disease initiation and progression
are moderated by systemic risk factors that modulate
destructive immunopathologic factors and flora, and
local risk factors that mainly contribute to dental bio-
film accumulation and retention.
V. Periodontitis and other systemic diseases inter-
act, often in both directions.
VI. Periodontal diseases, gingivitis and periodonti-
tis, are largely preventable and are able to be treated
successfully.
These pillars are well documented in the 150+ pa-
pers cited in Kornman et al.,1 as well as by a large body
of peer-reviewed robust supportive studies, some of
which are described in the Centennial Commentaries
recently published in the Journal of Periodontology.
It is clear then that we have a detailed under-
standing of periodontal disease as a common infec-
tion; we recognize many of the causative organisms
* Distinguished Professor of Oral Biology and Microbiology, State University
of New York at Buffalo; Vice Provost, Office of Science, Technology Transfer,
and Economic Outreach, Amherst, NY.
1308
and the immunopathologic processes leading to
tissue destruction. We also have a sound scientific
basis for prevention of gingivitis and periodontitis,
along with well-studied protocols for resolving the
infection and inflammation associated with both con-
ditions; and we have a reasonable understanding
of the possibilities for, and limitations of, regenerat-
ing soft and hard tissues lost to periodontitis. In cases
where there has been excessive periodontal tissue
destruction leading to loss of teeth, we have well-
documented studies of endosseous dental implants
as functional replacements.
FUTURE RESEARCH THEMES
Despite our current knowledge, there are several
areas where we need rigorous studies to further our
ability to manage periodontal diseases. Four areas
have been selected out of several possible themes for
future research. Recent advances in each of these
themes lead to study of testable hypotheses that may
result in clinical measures to better manage peri-
odontal diseases. These include:
A) Common Risk Factor Modification
There is mounting scientific evidence to propose
that modification of common risk factors by dental
practitioners is a strategy for controlling some of the
major chronic diseases of man. There is a set of risk
factors common to several chronic diseases including
periodontal disease, caries, cardiovascular disease,
diabetes, and cancer, and it has been proposed that
modification of these risk factors may lead to better
oral as well as general health.3
Risk factors for periodontal disease have been
reviewed recently by Genco and Borgnakke.4 We
reported that the strongest evidence for periodontal
risk factors exists for smoking, diabetes, and obesity.
Smoking, for example, has been found to be an in-
dependent risk factor for periodontal disease after
correcting for confounding factors such as oral hy-
giene and dental plaque levels. Even mild smok-
ing increases the odds 4- to 5-fold for periodontitis
and alveolar bone loss.5,6 Diabetes, both type 1
and type 2, are risk factors for periodontitis, espe-
cially when glycemic control is poor.7 Obesity and
doi: 10.1902/jop.2014.140346
J Periodontol October 2014
metabolic syndrome are also related to risk for peri-
odontal disease.7
Modifiable risk factors for diabetes include smok-
ing, being overweight or obese, and having hyper-
glycemia.3,8,9 Modifiable risk factors for many forms
of cancer include tobacco consumption, diabetes,
and obesity.10 Modifiable risk factors for heart disease
include tobacco exposure, obesity, and unhealthy
diets, and for stroke include cigarette smoking and
being overweight or obese.11
It is clear that smoking and obesity are common
risk factors for periodontal disease, diabetes, car-
diovascular diseases, stroke, and some forms of
cancer. Hence, common risk factor modification is
a potentially potent strategy for affecting these dis-
eases of man. We can engage the dental profession,
with the lead coming from periodontists, to carry out
the appropriate risk factor management for smoking
cessation and weight management. Reduction of
weight is a clear goal, but it may be that the dental
profession can initially help by continuing to rec-
ommend reduction of refined sugar consumption.
Studies to support the value of common risk factor
management, including large randomized clinical
trials to test the effectiveness of these means, as well
as behavioral studies and studies with new models of
interprofessional practice, may be necessary to
achieve the goal of effective reduction of smoking
and obesity as major lifestyle changes contributing to
good oral and general health.
B) Biofilm Inhibition and Dispersion
Biofilms are surface-associated microbial commu-
nities associated with a majority of infections of man
including caries, periodontal disease, implant and
catheter infections, and infections on damaged heart
valves and in the respiratory and genitourinary tracts.
Biofilms form in a sequential process initiated by
attachment of cells to a surface such as the salivary
pellicle-coated tooth. This initial phase is followed
by formation and maturation of a matrix-enmeshed
collection of microbial colonies, culminating in dis-
persion of bacteria from the mature biofilm. The
organisms dispersed from the biofilm then start the
process of conversion from the planktonic or free-
cell stage to form biofilms.12 This process occurs in
the oral cavity, resulting in dental plaques which
cause dental caries and periodontal diseases. The
control of biofilms has been difficult due to their
tenacious attachment to the tooth and resistance
to antibiotics and microbicides, as well as their
unique virulence.12,13 There is much known about
the initial stages including mechanisms of bacte-
rial adherence to salivary components, bacterial
bacterial interaction, and adherence-promoting matrix
production in dental plaques. Cell-to-cell signal
Genco
translation systems, through quorum sensing, are
thought to be responsible for genetic control of many
factors important to biofilm formation, antibiotic re-
sistance, and virulence.12 Attempts to inhibit these
initial events or to interfere with quorum sensing to
prevent dental plaque biofilm formation have been
disappointing to date.
Recognition of cell detachment or biofilm dispersal
as an important occurrence in mature biofilms, and
identification of cis-2-decenoic acid as a diffusible
factor that can induce biofilm dispersion, have led to
hypotheses that biofilm dispersion is a potentially
important new approach to control biofilms.13 Further
study of the mechanisms of action of cis-2-decenoic
acid and its in vivo effectiveness, clinical efficacy,
and safety profile is necessary before this approach
can be used clinically. This and other biofilm dispersal
agents such as nitric oxide14 and dispersin B15 rep-
resent novel and promising approaches to control
dental plaques associated with periodontal disease
and caries and other biofilm-associated diseases.
C) The Oral Microbiome
The microbial etiology of periodontal disease has
been studied for more than a century using mi-
croscopic and cultural techniques. The recent ad-
vent of DNA sequencing techniques, especially
next-generation sequencing of the 16S rRNA bac-
terial gene, which allows enumeration of entire
bacterial communities without culture, has revealed
several potential periodontal pathogens previously
unrecognized. For example, it has been estimated
using the DNA-sequencing techniques, that about
40% of the oral flora are novel species or phylotypes
not previously recognized by culture.16,17 Studies
reviewed by Teles and coworkers16 reveal that in
addition to the cultivable organisms previously re-
lated to periodontitis such as Porphyromonas gingi-
valis, Tannerella forsythia, and Treponema denticola,
there are more than 20 newly recognized organisms
that are found at significantly higher levels in peri-
odontal pockets than in the healthy subgingival flora.
Many of these newly recognized periodontal bacteria
are presently uncultivable, including several species
of the spirochete Treponema. Many are fastidious and
difficult to culture and therefore were not previously
recognized as being prominent members of the
periodontal pocket flora. These include Dialister
pneumosites, which has the potential to cause dis-
ease in the lung, brain, and dental root canals as well as
the periodontium.18,19 Another organism that was
missed or detected at low levels by culture, and is a
major component of the subgingival periodontal
microflora by 16S rRNA assessment, is Filifactor
alocis.20 It is often the second-most prevalent organism
in periodontitis pockets, is rarely found in healthy
1309
The Evolution of Periodontology
flora, and is localized at the biofilmgingival tissue
interface, suggesting it is at least a periodontal disease
marker, if not a causative agent in periodontitis.20
Other newly recognized bacteria prominent in
periodontal pockets which may be pathogens include
Porphyromonas endodontalis, Prevotella denticola,
Cryptobacterium curtum, Eubacterium saphenum,
Mogibacterium timidum, Prevotella sp., Peptos-
treptococcus magnus, Slakia exigua, Treponema
sp., Enterococcus faecalis, and Bartonella sp.16 It is
not clear which are truly pathogenic, or secondary
invaders. Alternatively, periodontal disease may
result from dysbiosis of the subgingival flora, and
restoration of healthy microbiome may be an ef-
fective mode of therapy. Much research directed at
determining their virulence, host responses to these
organisms, and effects of eradication or suppression
is necessary before they can be considered as part
of the polymicrobial complex(es) associated with
periodontal disease. Such studies establishing the
role of these newly recognized organisms may lead
to new and novel approaches to prevention and
treatment of periodontal diseases and possibly sys-
temic conditions associated with periodontal dis-
ease, such as diabetes and cardiovascular diseases.
The mobile microbiomes. The relationship of oral
infections and adverse systemic conditions is a
game changer and has received considerable at- over dental sources and bone marrow. Autogenous
tention from the biomedical community. There is
mounting evidence supporting the role of the sys-
temic dissemination of oral commensals and patho-
gens to sites including carotid atheromas, the placenta
and fetus, colon tumors, and the respiratory tract.21
These studies point to the importance of this line
of investigation in understanding the association of
periodontal disease with cardiovascular disease, ad-
verse pregnancy outcomes, some cancers and re-
spiratory infections. It is likely that detailed knowledge
of the mechanisms of translocation and virulence
mechanisms of the mobile oral microbiome may lead
to new approaches to managing periodontal disease,
and at the same time reduce the burden of associated
diseases. It is reasonable to propose that procedures
and medications directed at minimizing the translocation
of oral organisms to distant sites will result in not only
better oral health but also better general health.
D) Stem CellBased Tissue Engineering
One of the goals of periodontal therapy is to achieve
periodontal regeneration with reconstitution of lost
periodontal attachment structures. Extensive re-
search exists on the use of autografts, allografts, and
xenografts to promote periodontal regeneration, and
recently guided tissue regeneration (GTR) has be-
come a widely accepted regenerative procedure.22
There is concern that various grafting and GTR
1310
Volume 85 Number 10
procedures are mainly effective in select lesions that
have vertical or contained defect components and
are not as effective where horizontal regeneration of
alveolar bone is needed.23,24 Given this limitation
of current periodontal regenerative procedures and
their unpredictability, attention has been directed to
cell-based tissue engineering procedures.25
Stem cells have been prominent in the search
for better periodontal regenerative procedures as
these cells have the potential to differentiate into
cells that can restore the tissues needed for peri-
odontal regeneration including cementum, con-
nective tissue, bone, and other components of the
periodontium. Stem cells studied to date for peri-
odontal regeneration are largely adult stem cells,
mainly mesenchymal stem cells from bone marrow
or from dental sources such as the dental pulp,
shed deciduous teeth, apical papilla of developing
permanent teeth, or periodontal ligament stem cells.
A review of these stem cells and their use in regenerat-
ing dental tissues is provided by Huang et al.26 En-
couraging results from animal studies suggest use of
such dental stem cells once appropriate delivery de-
vices are developed and validation of safety profiles
is carried out in preparation for human trials.
Adipose-derived stem cells (ADS). Adipose tissue
as a source of stem cells offers several advantages
stem cells from adipose tissue can be readily obtained
from each patient, overcoming the possible immu-
nologic rejection phenomena likely with allogeneic
stem cells. Adipose-derived stem cells (ADS) have
been extensively studied for osteogenic differenti-
ation capacity and proposed for tissue-engineered
periodontal regeneration.27-29 A tissue-engineering
approach for periodontal regeneration using adipose-
derived autogenous stem cells has recently been
carried out using in vitro models.30 The results are
encouraging. The investigators were able to develop
a biodegradable 3-D scaffold composed of starch
and poly-E-(caprolactone) that promoted osteogenic
proliferation of the adipose-derived stem cells. In
another study, in vivo bone regeneration was achieved
with osteogenic, differentiated human adipose-
derived stem cells in a poly-lactide-co-glycolic scaf-
fold.31 A study of combinations of adipose-derived
autogenous stem cells, growth factors, and resorbable
scaffolds which showed success in reconstruction of
large craniofacial defects points the way to uses in
periodontal regeneration.32 However, much remains
to be done before such a system can be considered
for routine use. The ready accessibility of autogenous
adipose-derived stem cells and their osteogenic po-
tential at the least provide the basis to propose these
as candidates for effective periodontal regeneration
in the future.
J Periodontol October 2014
CONCLUSION
In conclusion, much progress has been made in
periodontology in the last 100 years, and we cele-
brate this progress in this 100th anniversary year of
the founding of the American Academy of Peri-
odontology. There are, of course, gaps remaining in
our knowledge about periodontal disease and its
management; however, ongoing scientific advances
continue to provide clues where concepts and hy-
potheses can be tested to fill these gaps.
We can look confidently to the future as rigorous,
fundamental and applied research, carried out by
dedicated and talented scientists and clinicians, will
continue to unravel the mysteries of a ubiquitous
disease. Periodontology is continuously evolving,
and the exciting promises of the future will depend
on science.
ACKNOWLEDGMENT
The author reports no conflicts of interest related to
this commentary.
REFERENCES
1. Kornman KS, Robertson PB, Williams RC. The litera-
ture that shaped modern periodontology. J Periodontol
2014;85:3-9.
2. Eke PI, Dye BA, Wei L, et al. Self-reported measures
for surveillance of periodontitis. J Dent Res 2013;92:
1041-1047.
3. Genco RJ, Genco FD. Common risk factors in the
management of periodontal and associated systemic
diseases: The dental setting and interprofessional col-
laboration. J Evid Based Dent Pract 2014;14(Suppl):
4-16.
4. Genco RJ, Borgnakke WS. Risk factors for periodontal
disease. Periodontol 2000 2013;62:59-94.
5. Grossi SG, Genco RJ, Machtei EE, et al. Assessment of
risk for periodontal disease. II. Risk indicators for
alveolar bone loss. J Periodontol 1995;66:23-29.
6. Grossi SG, Zambon JJ, Ho AW, et al. Assessment of
risk for periodontal disease. I. Risk indicators for
attachment loss. J Periodontol 1994;65:260-267.
7. Alpagot T, Wolff LF, Smith QT, Tran SD. Risk
indicators for periodontal disease in a racially diverse
urban population. J Clin Periodontol 1996;23:982-988.
8. American Diabetes Association. American Diabetes
Association announces 2014 legislative and regula-
tory priorities. Available at: http://www.diabetes.org/
newsroom/press-releases/2013/2014-legislative-priorities.
html. Accessed December 23, 2013.
9. Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J.
Active smoking and the risk of type 2 diabetes: A
systematic review and meta-analysis. JAMA 2007;
298:2654-2664.
10. Eyre H, Kahn R, Robertson RM; American Cancer
Society, the American Diabetes Association, and the
American Heart Association Collaborative Writing
Committee. Preventing cancer, cardiovascular disease,
and diabetes: A common agenda for the American
Cancer Society, the American Diabetes Association,
Genco
and the American Heart Association. Diabetes Care
2004;27:1812-1824.
11. Mayo Clinic. Diseases and conditions: Transient ischemic
attack (TIA). Available at: http://www.mayoclinic.org/
diseases-conditions/transient-ischemic-attack/basics/
risk-factors/CON-20021291. Accessed June 10, 2014.
12. Stoodley P, Sauer K, Davies DG, Costerton JW. Bio-
films as complex differentiated communities. Annu
Rev Microbiol 2002;56:187-209.
13. Davies DG, Marques CN. A fatty acid messenger is
responsible for inducing dispersion in microbial bio-
films. J Bacteriol 2009;191:1393-1403.
14. Li Y, Heine S, Entian M, Sauer K, Frankenberg-Dinkel
N. NO-induced biofilm dispersion in Pseudomonas
aeruginosa is mediated by an MHYT domain-coupled
phosphodiesterase. J Bacteriol 2013;195:3531-3542.
15. Stacy A, Everett J, Jorth P, Trivedi U, Rumbaugh KP,
Whiteley M. Bacterial fight-and-flight responses en-
hance virulence in a polymicrobial infection. Proc Natl
Acad Sci USA 2014;111:7819-7824.
16. Teles R, Teles F, Frias-Lopez J, Paster B, Haffajee A.
Lessons learned and unlearned in periodontal micro-
biology. Periodontol 2000 2013;62:95-162.
17. Albandar JM, Kingman A, Lamster IB. Crevicular fluid
level of beta-glucuronidase in relation to clinical peri-
odontal parameters and putative periodontal patho-
gens in early-onset periodontitis. J Clin Periodontol
1998;25:630-639.
18. Ghayoumi N, Chen C, Slots J. Dialister pneumosintes,
a new putative periodontal pathogen. J Periodontal
Res 2002;37:75-78.
19. Colombo APV, Boches SK, Cotton SL, et al. Compar-
isons of subgingival microbial profiles of refractory
periodontitis, severe periodontitis, and periodontal
health using the human oral microbe identification
microarray. J Periodontol 2009;80:1421-1432.
20. Schlafer S, Riep B, Griffen AL, et al. Filifactor alocis
involvement in periodontal biofilms. BMC Microbiol
2010;10:66.
21. Han YW, Wang X. Mobile microbiome: Oral bacteria in
extra-oral infections and inflammation. J Dent Res
2013;92:485-491.
22. Karring T, Nyman S, Gottlow J, Laurell L. Development
of the biological concept of guided tissue regeneration
Animal and human studies. Periodontol 2000 1993;1:
26-35.
23. Pontoriero R, Lindhe J. Guided tissue regeneration in
the treatment of degree III furcation defects in maxillary
molars. J Clin Periodontol 1995;22:810-812.
24. Wallace SC, Gellin RG, Miller MC, Mishkin DJ. Guided
tissue regeneration with and without decalcified freeze-
dried bone in mandibular Class II furcation invasions.
J Periodontol 1994;65:244-254.
25. Hynes K, Menicanin D, Gronthos S, Bartold PM. Clinical
utility of stem cells for periodontal regeneration. Peri-
odontol 2000 2012;59:203-227.
26. Huang GTJ, Gronthos S, Shi S. Mesenchymal stem
cells derived from dental tissues vs. those from other
sources: Their biology and role in regenerative medi-
cine. J Dent Res 2009;88:792-806.
27. Tobita M, Uysal AC, Ogawa R, Hyakusoku H, Mizuno H.
Periodontal tissue regeneration with adipose-derived
stem cells. Tissue Eng Part A 2008;14:945-953.
28. Vieira NM, Brandalise V, Zucconi E, Secco M, Strauss
BE, Zatz M. Isolation, characterization, and differenti-
ation potential of canine adipose-derived stem cells.
Cell Transplant 2010;19:279-289.
1311
The Evolution of Periodontology Volume 85 Number 10

29. Requicha JF, Viegas CA, Albuquerque CM, Azevedo
JM, Reis RL, Gomes ME. Effect of anatomical origin
and cell passage number on the stemness and osteo-
genic differentiation potential of canine adipose-
derived stem cells. Stem Cell Rev 2012;8:1211-1222.
30. Requicha JF, Viegas CA, Mun oz F, et al. A tissue
engineering approach for periodontal regeneration
based on a biodegradable double-layer scaffold and
adipose-derived stem cells [published online ahead of
print April 22, 2014]. Tissue Eng Part A. doi:10.1089/
ten.tea.2013.0360.
31. Yoon E, Dhar S, Chun DE, Gharibjanian NA, Evans
GR. In vivo osteogenic potential of human adipose-
derived stem cells/poly lactide-co-glycolic acid con-
structs for bone regeneration in a rat critical-sized
calvarial defect model. Tissue Eng 2007;13:619-
627.
32. Sandor GK. Tissue engineering of bone: Clinical obser-
vations with adipose-derived stem cells, resorbable
scaffolds, and growth factors. Ann Maxillofac Surg
2012;2:8-11.
Correspondence: Dr. Robert J. Genco, University at
Buffalo, Office of Science, Technology Transfer, and
Economic Outreach, Baird Research Park, 1576 Sweet
Home Road, Suite 103, Amherst, NY 14228. Fax: 716/
636-5921; e-mail: rjgenco@buffalo.edu.
Submitted June 10, 2014; accepted for publication June
10, 2014.

Editors Note: Please refer to J Periodontol 2014;85:1-2 for an introductory commentary by Kornman,
Robertson, and Williams explaining the AAP Centennial Commentaries, and to J Periodontol 2014;85:3-9 for
a comprehensive reading list of peer-reviewed papers (organized by theme) that helped shape the modern
practice of periodontics and current knowledge in periodontology.

AAP Members: Want to discuss any of the topics covered in the Centennial Commentaries? Share your
thoughts with your peers on AAP Connects Open Forum at Perio.org > Member Resources > AAP Connect.

1312