Growth Factors

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Role of growth factors on periodontal repair

X. E. Dereka, C. E. Markopoulou & I. A. Vrotsos

To cite this article: X. E. Dereka, C. E. Markopoulou & I. A. Vrotsos (2006) Role of growth factors
on periodontal repair, Growth Factors, 24:4, 260-267, DOI: 10.1080/08977190601060990

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Growth Factors, December 2006; 24(4): 260–267

Role of growth factors on periodontal repair

X. E. DEREKA, C. E. MARKOPOULOU & I. A. VROTSOS

1
Department of Periodontology, School of Dentistry, University of Athens, Athens, Greece

(Received 22 March 2006; revised 9 October 2006; accepted 10 October 2006)

Abstract
Regeneration of periodontal structures lost during periodontal diseases constitutes a complex biological process regulated
among others by interactions between cells and growth factors. Growth factors are biologically active polypeptides affecting
the proliferation, chemotaxis and differentiation of cells from epithelium, bone and connective tissue. They express their
action by binding to specific cell-surface receptors present on various target cells including osteoblasts, cementoblasts and
periodontal ligament fibroblasts. The observation that growth factors participate in all cell functions led to exogenous
application during periodontal tissue repair aiming to their use as an alternative therapeutic approach to periodontal therapy.
Cell types and cultures conditions, dose, carrier materials, application requirements are of critical importance in the outcome
of periodontal repair. The purpose of this article is to review the literature with respect to the biological actions of PDGF,
TGF, FGF, IGF and EGF on periodontal cells and tissues, which are involved in periodontal regeneration.

Keywords: Growth factors, periodontal repair, periodontal tissues, periodontal defects, therapeutic application

Introduction the use of different grafting materials and their

Periodontitis is an inflammatory disease characterized
by destruction of periodontal ligament, root cemen-
tum and alveolar bone as a tissues response to
microbial plaque accumulation on the tooth root
surface. The repair of the periodontal structures
constitutes a complex biological process regulated,
among other, by interactions between cells and growth
factors as well as between hormones and growth
factors triggering a series of cellular events leading to
tissue formation.
Periodontal therapy that aims at the regeneration of
the periodontal tissues, i.e. the restoration of their
initial form, architecture and function, is not achieved
in a predictable pattern. Different cell types, cellular
activity, microbial and cytokine environment as well as
host response play an important role. Therefore, a
wide range of therapeutic procedures has been
developed to attain this primary goal. Periodontal
treatment includes conventional methods such as
scaling and root planing, periodontal surgery with or
without osseous surgery and new approaches such as
root conditioning agents, guided tissue regeneration,
combination.
Advances in molecular and cellular biology led to
the study of growth factors’ potential role in
promoting periodontal regeneration and their use as
an alternative therapeutic approach.
Growth factors are biologically active polypeptide
hormones, which affect the immune function as well
as the proliferation, chemotaxis and differentiation of
cells from the epithelium, bone and connective tissue
(Bartold et al. 2000). They bind to specific cell-
surface tyrosine kinases receptors (Terranova and
Wikesjo 1987; Rosenkranz and Kazlauskas 1999),
which are present on various target cells including
osteoblasts, cementoblasts and periodontal ligament
(PDL) fibroblasts (Howell et al. 1996). The effect of
growth factors on the different cell lines seems to
depend on the quantity used and the type of carrier
that the growth factor is combined with, affecting also
their release time.
Platelet-rich plasma (PRP) which consists of a
concentrated suspension of growth factors has been
demonstrated to induce healing and regeneration of

Correspondence: X. E. Dereka110 Vas. Sofias Str., Athens, Greece. Tel: 30 210 7773037. Fax: 30 210 7773038. E-mail: dereka@otenet.gr

ISSN 0897-7194 print/ISSN 1029-2292 online q 2006 Informa UK Ltd.

DOI: 10.1080/08977190601060990

the periodontal tissues. It is a storage vehicle especially
for PDGF and TGF-b. A new easy procedure to
create PRP has been developed. Consequently, the
preparation and application of PRP can be accom-
plished in dental clinic and the beneficial outcomes of
the autologous product could be suggested as suitable
agent in the treatment of periodontal defects (Tözüm
and Demiralp 2003).
The purpose of this article is to review the literature
concerning the main biological actions of PDGF,
TGF, FGF, IGF and EGF on periodontal cells and
tissues. Thus, it is an attempt to summarize the results
of the in vitro and in vivo studies demonstrating the
major role of these growth factors on periodontal
repair.
Platelet-derived growth factor (PDGF)
Platelet-derived growth factor (PDGF) is primary
secreted from the platelets but also from the activated
macrophages and fibroblasts and contains two
polypeptide chains forming three isoforms either as a
homodimer (AA or BB) or as a heterodimer (AB).
Research data indicated that PDGF A and B chains
are present in gingival epithelium with PDGF-A
playing an important role during early stages of wound
healing process while PDGF-B appears later (Green
et al. 1997).
The biological effects of PDGF are mainly initiated
via two tyrosine kinases receptors termed alpha and
beta PDGF receptors (Rosenkranz and Kazlauskas
1999) which are differentially expressed by normal
and regenerating periodontal cells indicating that
PDGF is involved in a complex pattern in healing
events (Parkar et al. 2001). PDGF-receptors
(PDGFR-a, -b) can be degraded via direct proteolysis
on the cell surface by elastase, which is an essential
factor for host defense and has the ability to degrade
extracellular matrix proteins and this fact would not
be advantageous for periodontal regeneration
(Nemoto et al. 2005).
Recently, two more isoforms are identified PDGF-
C and -D, which exert their function binding to alpha-
and beta-receptor respectively (Li et al. 2000;
Bergsten et al. 2001). PDGF is a potent mitogen for
cells of mesenchymal origin including fibroblasts
(Oates et al. 1993; Boyan et al. 1994).
The effect of recombinant human platelet-derived
growth factor individually, as well as, in combination
with other growth factors like TGF-b, IGF-I and EGF
was examined on rat periodontal ligament fibroblastic
(Matsuda et al. 1992). The results indicated a strong
mitogenic and chemotactic cell response to PDGF,
which also stimulated collagen synthesis by PDL cells.
Furthermore, it was found that PDGF-BB isoform is
more effective than PDGF-AA and PDGF-AB in
promoting PDL cells mitogenesis, in vitro (Boyan et al.
1994).
Growth factors on periodontal repair 261
PDGF-BB at the concentration of 10 and 20 ng/ml
could enhance in vitro the osteoblasts proliferation but
had no effect on the differentiation of these cells
(Strayhorn et al. 1999), while the optimal PDGF-BB
concentrations stimulating PDL cells adherence to
periodontal diseased root surfaces found equal or
greater than 50 ng/ml (Gamal and Mailhot 2000).
Applied to EDTA demineralised dentin surfaces
PDGF-BB promoted human PDL cells proliferation
(Zaman et al. 1999) and increased cementoblasts
mitogenesis affecting a range of events required for
periodontal tissues regeneration (Saygin et al. 2000).
Concerning the effect of PDGF-BB on PDL cells
and gingival fibroblasts the data indicated variable
responses of fibroblasts to growth factor depending
upon the anatomical site within the periodontium
(Haase et al. 1998). There are cell-specific differences
critical to periodontal wound healing such as the
significant stimulation of PDL cells proliferation
whereas gingival fibroblasts seemed to respond
primarily through cell migration (Mumford et al.
2001).
In addition, as the results from our previous study
indicated, PDGF-BB at a concentration of 10 ng/ml
acts like a strong mitogenic agent for human PDL cells
and gingival fibroblasts (Markopoulou et al. 2003).
PDGF-BB may act as a regulator of the extracellular
matrix maintenance, significantly stimulating collagen
synthesis by the human PDL fibroblasts (Boltchi et al.
1999) exhibiting an inverse time- and dose-dependent
effect (Ojima et al. 2003).
The synergistic effect of PDGF combined with
other growth factors revealed the highest cell
responses in parameters of periodontal tissues healing.
The combination of different growth factors resulted
in stimulating effects on different metabolic functions
of osteoblasts. The researchers found that the
combination of PDGF-BB with IGF or TGF-b1
showed synergistic effect on osteoblasts activity
enhancing cell proliferation greater than the effects
of the single growth factors (Giannobile et al. 1997;
Mott et al. 2002). In an attempt to investigate, the
beneficial role of rhPDGF-BB/IGF-I combination as
well as the safety and the proper dose in order to
achieve periodontal regeneration, 50 and 150 mg/ml
each of these growth factors were applied in human
osseous defects. The results indicated promotion of
bone regeneration by the highest dose of rhPDGF-
BB/IGF-I (Howell et al. 1997). PDGF-BB and IGF-I
were added to extraction pockets in dogs to stimulate
differentiation, migration and extracellular synthesis
of cells involved in the healing socket events. The graft
tissue resulted with better reparative capacities was
then used to treat class II furcation bone defects. The
findings did not reveal any statistical difference
between control and test groups but indicated a
potential use of this type of graft in the treatment of
periodontal lesions (Soares et al. 2005).
262 X. E. Dereka et al.
PDGF-BB highly expressed in epithelium and
connective tissue of human inflamed gingival
(Pinheiro et al. 2003) was also studied, in vitro, in
combination with two demineralized and one non-
demineralized freeze-dried bone allografts and it was
demonstrated the beneficial role of these grafting
materials as carrier agents for PDGF-BB, to perio-
dontal regeneration (Papadopoulos et al. 2003).
Furthermore, rhPDGF-BB incorporated in
DFDBA resulted in a complete new attachment
apparatus in human class II furcations defects, which
was confirmed clinically and histologically (Camelo
et al. 2003; Nevins et al. 2003). A large-scale
randomized controlled clinical trial evaluating the
safety and efficacy of PDGF-BB for the treatment of
periodontal osseous defects demonstrates that
rhPDGF-BB combined with a synthetic beta-trical-
cium phosphate matrix significantly increased the
clinical attachment level, reduced gingival recession
and improved bone fill (Nevins et al. 2005; Reynolds
and Aichelmann-Reidy 2005).
Moreover, recent clinical studies in humans
investigate the effect of rhPDGF-BB on bone turnover
during periodontal repair and periodontal wound
repair. Data indicate a direct effect on the pyridinoline
cross-link of type I collagen (ICTP), a biomarker of
bone turnover, released from the wound, mainly
during the early stages of tissue repair. Contrasting
results have been found at the expression of wound
fluid levels of PDGF-AB, VEGF and ICTP during
periodontal healing when PDGF-BB is delivered to
promote periodontal tissue engineering (Cooke et al.
2006; Sarment et al. 2006).
Many researchers investigated the potential of
PDGF gene therapy for periodontal engineering. It
was demonstrated that PDGF gene delivery enhanced
the proliferative response of all periodontal cells and
further stimulated cementoblast activity and alveolar
bone and cementum regeneration in rat periodontal
defects (Giannobile et al. 2001; Zhu et al. 2001; Jin
et al. 2004).
The data of the in vitro and in vivo published studies
imply that PDGF-BB either individually or combined
with other growth factors and especially with IGF is
probably the most cell mitogenic agent.
Transforming growth factor-beta (TGF-b)
Transforming growth factor-b (TGF-b) represents a
family of polypeptide growth factors related to bone
morphogenetic proteins (BMPs) but functionally
different (Howell et al. 1996; Lee 1997) involved in
embryogenesis, inflammation and regulation of
immune response, and wound healing (Scaleric et al.
1997).
Three mammalian TGF-b isoforms, TGF-b1,
TGF-b2 and TGF-b3, encoded by three distinct
genes and structurally identical, are synthesized by
platelets, macrophages, fibroblasts and tumor cells
(Javelaud and Mauviel 2004) with type 1 isoform
being the most abundant (Roberts 2000). In period-
ontally affected tissues, increased levels of TGF-b2
and TGF-b3 were detected compared to healthy
tissues while no evidence of TGF-b1 was revealed (Ye
et al. 2003).
The TGF-b receptors were detected by chemical
cross linking of the cell surface binding proteins and
the electrophoretic separation revealed three types of
proteins named types I, II and III. TGF-b signals in
most cases through the same serine-threonine kinase
type I and II cell surface receptors (Derynck and Feng
1997). The location of TGF-b receptors types II and
III on the cell membrane surface and cytoplasm of the
forming rat periodontal ligament as well as on the
extracellular matrix suggest that TGF-b interacts with
target cells during development and maturation of the
periodontium (Gao et al. 1999). Furthermore, TGF-
b receptors are differentially expressed in periodontal
tissues and cells and are increased in regenerated
tissue suggesting that are involved in wound healing
and periodontal repair process (Parkar et al. 2001).
TGF-b is considered as a chemotactic agent for
bone cells, increases matrix production and increases
or decreases their proliferation depending on the cell
differentiation state, the culture conditions and the
TGF-b concentration used (Cochran and Wozney
1999). TGF-b exerts its effects on cell proliferation,
differentiation, migration partly due to its ability to
modulate the deposition of extracellular matrix
components (Verrecchia and Mauviel 2002).
TGF-b1 is expressed during the development of the
alveolar bone, PDL and cementum as well as through
all stages of dental formation in the osteoblasts, PDL
cells and cementoblasts close to the apical portion of
root (Gao et al. 1998). The research results indicated
that TGF-b1 is released from human cultured gingival
epithelial sheets in significant amounts suggesting that
may promote wound healing and periodontal tissue
regeneration (Momose et al. 2002).
It was also found that in vitro TGF-b1 mostly
supports the proliferation of human PDL and gingival
fibroblasts at the concentration of 10 ng/ml after 48 h
of cell culture (Markopoulou et al. 2003).
TGF-b stimulated PDL regeneration and repair by
increasing SPARC (secreted protein acidic and rich in
cytokine/osteonectin), DNA and fibronectin levels in
PDL cells (Fujita et al. 2004) but suppressed the
osteoblast-like phenotype of human PDL cells (Brady
et al. 1998; Fujita et al. 2004).
Concerning TGF-b1 participation to matrix main-
tenance, it is indicated that stimulates type I collagen
synthesis (Brady et al. 1998) depending on the
experiment conditions, the cell line and the stage of
the cell development (Javelaud and Mauviel 2004).
Furthermore, TGF-b1 decreases the synthesis of
matrix metalloproteinases and plasminogen activator,

which increases synthesis of TIMP and plasminogen
activator inhibitor, resulting in a decrease of connec-
tive tissue matrix destruction (Javelaud and Mauviel
2004).
In an animal model, TGF-b1 production by rat
osteoblasts was enhanced in the presence of PepGen
P-15 (Trasatti et al. 2004).
In an in vitro wound healing assay it was
demonstrated that Porphyromonas gingivalis infection
obstructs wound repair process in PDL cells
stimulated by enamel matrix derivative (EMD)
which has been shown to promote attachment and
growth of PDL cells and production of TGF-b1 and
IGF-I as well (Inaba et al. 2004).
The in vivo regenerative potential of TGF-b,
considering the published data, is rather equivocal
and contradictory. The application of rhTGF-b1
combined with guided tissue regeneration (Wikesjo
et al. 1998) as well as following surgical implantation
(Terranova et al. 1989) in beagle dogs’ osseous defects
resulted in a limited alveolar bone and cementum
regeneration. Furthermore, it was also demonstrated
the beneficial role of TGF-b1 in conjunction with a
barrier membrane in class II furcation defects in
sheep (Mohammed et al. 1998) and its effective role in
promoting bone formation in dogs’ defects when
released slowly from a collagen sponge (Shigeno et al.
2002).
Taking account of the TGF-b1 multifunctional
properties, the increased expression of the growth
factor in the soft tissues around failing implants might
be beneficial in the maintenance of tissue homeostasis
(Cornelini et al. 2003).
TGF-b1 can be readily detected in the GCF and
has been found in increased levels following perio-
dontal surgery implying the potential use of the
changes of growth factors levels as a prognostic marker
of periodontal repair progress (Kuru et al. 2004).
The results of the studies indicate that the effect of
TGF-b on cell activities is rather ambiguous depend-
ing on the experiment conditions, the type of the
cellular population as well as the presence of other
growth factors.
Insulin-like growth factors (IGFs)
The family of insulin-like growth factors consists of
insulin and the peptides IGF-I, and IGF-II, which
bind to three separate receptors (Clemmons 2000).
They are natural biological mediators, which
regulate many of the cellular events and may enhance
periodontal wound healing and regeneration by
affecting the PDL cell turnover (Han and Amar
2003a,b). IGF-I exerts mitogenic effects on fibro-
blastic cell lines and appears to act as progression
factor inducing cell mitosis (Cochran and Wozney
1999) and as an important regulator of bone cell
metabolism (Giannobile et al. 1997).
Growth factors on periodontal repair 263
IGF-I promotes extracellular matrix synthesis and
proliferation of gingival fibroblasts and fibroblasts
deriving from regenerating soft connective tissue,
which additionally proliferate faster than PDL
fibroblasts (Ivanovski et al. 2001). In a recent study
the results showed that IGF-I stimulates human PDL
fibroblast proliferation in a dose-and time-dependent
manner but does not affect cell adhesion, migration
and expression of type I collagen (Palioto et al. 2004).
Cementoblasts, on the other hand, treated with IGF-I
show accelerated rate of proliferation and increased
bone sialoprotein gene expression while osteocalcin
and osteopontin gene expression is not affected
(Saygin et al. 2000).
It seems that normal periodontal tissues do not
express receptors of IGF and only weak and variable
expression has been noticed in the regenerated tissues
(Parkar et al. 2001). However, PDL fibroblasts and
cementoblasts of deciduous human teeth were found
to carry IGF-IR (Götz et al. 2001) which are
involved during mineralized nodule formation by
these cells (Nemoto et al. 2004). In a recent study,
researchers demonstrated that the components of the
IGF system could be immunohistochemically
detected in the rat periodontium. Moreover, the
majority of these components were localized in the
cells and matrix of the resorption lacunae after
experimentally tooth movement induction and
during reparative process after force removal imply-
ing that IGF system plays an important role in the
early repair events (Götz et al. 2006).
IGF-I can interact synergistically with other growth
factors such as PDGF-BB, TGF-b1 and bFGF and
enhance periodontal soft and hard tissues regener-
ation. Thus, the application of IGF-I/ PDGF-BB
combination in monkeys’ osseous defects resulted in
significant enhancement of new attachment and fill of
the defects revealing the synergistic effect of these two
growth factors on periodontal repair (Giannobile et al.
1996). Furthermore, in humans’ periodontal osseous
defects, the local application of the same combination
in a concentration of 150 mg/ml of each growth factor
resulted in a significant stimulation of bone regener-
ation (Howell et al. 1997).
The results of the studies apparently indicate that
IGF alone does not significantly influence the cellular
activities. IGF-I rather exerts its action as an
adjunctive agent mostly combined with PDGF.
Fibroblast growth factors (FGFs)
Fibroblast growth factors are members of a large
polypeptide family and considered as potent regula-
tors of cell growth and differentiation (Galzie et al.
1997; Davidson et al. 2005). FGFs family consists of
at least 18 genes and there are four distinct genes
encoding for their high-affinity receptors (Baird and
Ornitz 2000). The FGFs chemotactic and mitogenic
264 X. E. Dereka et al.
capability on cells of mesodermal origin as well as their
angiogenetic effect render these factors very important
during healing and repair of periodontal tissues. The
predominant FGF products are FGF-1 or acidic
(aFGF) and FGF-2 or basic (bFGF).
The receptor FGF-RI binds both aFGF and bFGF,
which function in mitogenesis, formation of extra-
cellular matrix and angiogenesis in vivo. No expression
of this receptor was found in human normal gingival
and PDL and only small amounts were found in
regenerated tissues (Parkar et al. 2001), while in a
previous study, the results indicated that bFGF
receptors are present in PDL cells but their density
can change during cell culture (Takayama et al. 1998).
Furthermore, bFGF can bind to other types of FGFR
in addition to FGF-RI and continues to influence cell
activities (Parkar et al. 2001).
FGFs are related with growth enhancement effect
mainly on fibroblast cell lines triggering angiogenesis,
cell migration and wound healing (Cochran and
Wozney 1999).
bFGF is produced primarily by fibroblast and
endothelial cells in human PDL and its levels are
decreased during chronic periodontal inflammation
(Gao et al. 1996). bFGF enhances PDL cells
proliferation but inhibits cell differentiation by
inhibition of cell alkaline phosphatase activity (Oka-
moto et al. 1997) and mineralized nodules formation
by these cells (Murakami et al. 1999).
bFGF has a dose-dependent migratory effect on
PDL cells and gingival fibroblasts (Nishimura and
Terranova 1996) and exhibits an inverse time- and
dose-dependent effect on PDL cells concerning the
gene expression of collagen I and MMP-1 (Palmon
et al. 2000). bFGF is trapped in the extracellular
matrix between gingival epithelium cells where it
adheres to heparansulfate proteoglycan playing an
important role in homeostasis, cytodifferentiation and
wound healing (Takayama et al. 2002). bFGF in vitro
found to enhanc the proliferation of human osteo-
blast-like cells while this effect was increased when it
was combined with DFDBA and DFBA (a Greek
allograft of cancellous origin) (Dereka et al. 2004).
Furthermore, bFGF plays in vitro an important role in
hyaluronan production by human PDL cells resulting
in induction of cell proliferation, enhancement of
structural component of extracellular matrix and
improvement of tissue repair (Shimabukuro et al.
2005).
In a histometric study bFGF found to promote
regeneration in dogs’ class III furcations defects,
which were filled with mineralized and non-miner-
alized tissues (Rossa et al. 2000). Further studies
indicated that bFGF considerably stimulated perio-
dontal regeneration in primate models) and in beagle
dogs’ class II furcation defects with no ankylosis or
root resorption observed, while combined treatment
with BMP-2 led to increased bone formation
(Murakami et al. 1999; Takayama et al. 2001;
Fijimura et al. 2002; Murakami et al. 2003). The
topical application of bFGF with fibrin glue in
delayed-replanted monkey teeth did not significantly
promote the complete healing although the inhibition
of replacement resorption could be speculated (Sae-
Lim et al. 2004).
In conclusion, bFGF seems to promote the
proliferation of PDL cells and osteoblasts in a dose-
dependent manner but does not provoke any
significant effect on cell differentiation.
Epidermal growth factor (EGF)
EGF is a small polypeptide growth factor found to be
involved in control of epithelial growth and differen-
tiation of periodontal tissues (Nordlund et al. 1991).
EGF and EGF-receptors which are transmembrane
tyrosine-kinase proteins activated by binding to the
growth factor (Schlessinger 2002), are localized in the
dental follicle, alveolar bone and ameloblasts implying
their important role at the stages before and during
tooth eruption (Shroff et al. 1996).
High levels of EGF and EGF-receptors were
detected in cells derived from healthy junctional
epithelium while PDL fibroblasts also express a large
number of EGF-receptors (Irwin et al. 1991; Tajima
et al. 1992; Garant 2003).
EGF appeared to enhance slightly chemotaxis and
to suppress matrix synthesis in rat PDL cells (Matsuda
et al. 1992). However, EGF restricted cell differen-
tiation and up-regulated EFG-R expression, which is
down regulated in the process of differentiation
(Matsuda et al. 1993). EGF receptors decrease
when cells differentiate into cell types capable of
forming mineralized tissues suggesting that EGF
receptors may participate in the phenotype stabiliz-
ation of PDL cells (Matsuda et al. 1993). The
interaction between mechanical stress and the
EGF/EGF-receptor system might participate in
the osteoblastic differentiation of human PDL cells
and regulate PDL as a source of cementoblasts and
osteoblasts (Matsuda et al. 1998a,b). The EGF/EGF-
receptor system promotes osteogenic cells prolifer-
ation but suppresses cell differentiation by ceasing the
expression of osteoblast markers (Chien et al. 2000).
EGF-R appeared to be present in very low amounts in
the gingival connective tissue and the epithelium of
normal gingiva, while increased levels of EGF-R were
observed in cells from regenerated tissues (Parkar et al.
2001).
The mitogenic response of human PDL cells to
EGF seems to be associated with the rapid and
selective activation of ERK (extracellular-related
kinase)1/2 pathway (Matsuda et al. 1998,b). In
addition, the results of a recent study showed that
EGF could support osteoblastic cells proliferation
(Winter et al. 2005).

On the other hand, PDL cells and gingival
fibroblasts exhibited dose-dependent migratory
response to EGF (Nishimura and Terranova 1996),
while EGF-binding capacity in human gingival tissue
found enhanced during inflammation compared to
that in non-inflamed gingiva. This observation might
be associated with a lower concentration of EGF in
gingival crevicular fluid (Chang et al. 1996). Increased
salivary EGF levels were transiently detected after
intra-oral wounding by periodontal surgery when
compared salivary samples pre- and postsurgically
(Oxford et al. 1998, 1999).
EGF down-regulated ALPase activity and SPARC
synthesis in human PDL cells while increased DNA
and fibronectin synthesis, suggesting that EGF might
act as a regulator of proliferation during periodontal
regeneration and repair (Fujita et al. 2004).
Furthermore, EGF stimulated urokinase-type plas-
minogen activator (uPA) expression in gingival
fibroblast suggesting that in different forms of
periodontal disease when EGF is up-regulated the
tissues proteolytic process is enhanced (Smith et al.
2004).
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