CONTENTS: Introduction Some basic terminologies Definition Rational for use in dentistry Effects of growth factors at various levels Mode of action of growth factors Receptors for growth factors Common features of growth factors Classification of growth factors Type of growth factors and actions Conclusion References INTRODUCTION: Periodontal diseases result in destruction of periodontal tissues, including cementum, bone, and periodontal ligament (PDL), with eventual tooth loss if left untreated. Traditional Method……Elimination of bacterial pathogens + Modulation of host response leads to Arrest / Slow disease progression. Better understanding of the disease at the cellular and molecular level as well as events involved in tissue development, healing and regeneration has Improved therapies with Arrest Of Disease Progression & Ultimate goal is to regenerate the periodontal tissues. SOME BASIC TERMINOLOGIES : Repair: Healing of a wound by tissue that does not fully restore the architecture or function of the part. (AAP, Glossary of periodontal terms, PAL). Repair simply restores the continuity of the diseased marginal gingiva and reestablishes a normal gingival sulcus at the same level on the root as the base of the preexistent periodontal pocket. This process called healing by scar, arrests bone destruction without necessarily increasing bone height (caranza). Regeneration: Is the growth and differentiation of new cells and intercellular substances to form new tissues or parts. Regeneration takes place by growth from the same type of tissue that has been destroyed or from it’s precursor. This is termed as wear and tear repair. Reattachment: The term has been used in past to refer to the restoration of the marginal periodontium. As per (AAP-92) it is defined as the reunion of epithelial and connective tissues with root surfaces and bone such as occur after an incision or injury. It should not be confused with new attachment. New attachment: is the embedding of new periodontal ligament fibers into new cementum and the attachment of the gingival epithelium to a tooth surface previously denuded by disease. Epithelial adaptation: Differs from new attachment in that it is the close apposition of the gingival epithelium to the tooth surface without complete obliteration of the pocket. PERIODONTAL REGENERATION is defined as the restoration of lost periodontium or supporting tissues and includes formation of new alveolar bone, new cementum and new periodontal ligament. There is a need, however, to improve the predictability of regenerative therapies. This need has led to increased efforts, to establish the specific cells, factors, delivery systems, flap design, and host responses required for enhancing outcome of regenerative therapies.

1. GROWTH FACTORS AND THEIR
RECEPTORS
GUIDED BY
DR K REKHA RANI
(PROF & HOD)
PRESENTED BY
R ANIL KUMAR PG-
II

2. CONTEN
TS
 Introduction
 Basic terminologies
 Definition
 Rational for use in dentistry
 Classification of growth factors
 Effects of growth factors at various cell cycles
 Mode of action of growth factors
 Receptors for various growth factors
 Common features of growth factors
 Individual growth factors and their actions
 Conclusion
 References

3. INTRODUCTION
 Periodontal diseases result in destruction of periodontal tissues,
including cementum, bone, and periodontal ligament (PDL), with
eventual tooth loss if left untreated.
 Goal of all therapeutic modalities is to Restore Health of Individual.
 Traditional Method……Elimination of bacterial pathogens
Modulation of host response
Arrest / Slow disease progression

4.  Better understanding of the disease at the cellular and molecular
level as well as events involved in tissue development, healing and
regeneration.
Improved therapies
Arrest Of Disease Progression
Ultimate goal of periodontal therapy
- REGENERATION

5. Basic
terminologies
Repair:
Healing of a wound
by tissue that does
not fully restore the
architecture or
function of the part.
(AAP)
Regeneration
Is the growth and
differentiation of new
cells and
intercellular
substances to form
new tissues or parts.
Reattachment:
it is defined as the
reunion of epithelial
and connective
tissues with root
surfaces and bone
such as occur after
an incision or injury.
New attachment:
is the embedding of
new periodontal
ligament fibers into
new cementum and
the attachment of
the gingival
epithelium to a tooth
surface previously
denuded by disease.

6. • PERIODONTAL REGENERATION is defined as the restoration of lost
periodontium or supporting tissues and includes formation of new alveolar
bone, new cementum and new periodontal ligament.
There is a need, however, to improve the predictability of regenerative
therapies.
This need has led to increased efforts, to establish the specific cells, factors,
delivery systems, flap design, and host responses required for enhancing
outcome of regenerative therapies.
 Although significant advances have been made toward understanding the
complexities involved in promoting periodontal regeneration, much remains
to be elucidated.

7.  Biologic modifiers are materials or proteins and factors that have the
potential to alter the host tissue, so as to stimulate or regulate the wound
healing process.
 Classic examples of biologic modifiers are growth factors.

8. DEFINITION
 GROWTH FACTORS: A diverse group of polypeptides that have
important roles in regulation of growth and development of a variety
of organs. – GPT
 GROWTH FACTORS: it is a general term used to denote a class of
naturally occurring proteins that function in the body to promote
mitogenesis, migration and metabolic activity. -Alan Polson

9. RATIONALE FOR USE IN DENTISTRY
Periodontal development
Disruption of ERS
Reorganization of cells
Between tooth & bone
Progenitor cells
PDL, Bone, Cementum
Periodontal regeneration
Clot formation
Granulation tissue
Progenitor cells
PDL, BONE,
CEMENTUM
Cells at site of marrow derived cells
tooth development
cell-cell & inflammatory response
cell matrix interactions (GFs &cytokines)
(GFs & cytokines)
Migration/attachment/orientation Migration/attachment/orientation
/proliferation factors / proliferation factors
Differentiation factors Differentiation factors

10. CLASSIFICATION
OF GROWTH
FACTORS
Divyanshu Jamwal, Pramod Waghmare. “Growth
factors in periodontal regeneration:
International Journal of Current Research.2018:10,
(09), 73439-73444.

12. Effect of growth factors at various levels of cell cycle
 The most fundamental process of tissue growth and development begins with
cell proliferation.
 Cells from different tissues grow and divide at quite different rates.
Cell
proliferation
There are four main phases of cell
cycle:
• S phase (synthesis phase)
• M phase (mitotic Phase)
• G1 and G2 phase (gap phases)
• G0 phase (resting phase)

13. Cell
differentiation
Differentiation is a process by which
undifferentiated cells transform into a specific
type of cell.
Differentiation brings about structural and
functional changes in the cell which are
necessary for the formation of type of tissue,
e.g., fibroblast for periodontal ligament,
osteoblast for bone, etc.
Growth factors will stimulate or inhibit cell
differentiation, exert their effect through
receptor binding and are thus described as
regulators of the cell cycle.
Growth factors play an important role in the
regeneration of periodontal tissues to stimulate
the migration, proliferation, and differentiation
of various cells that have the capacity to
regenerate the tissues.

14. MODE OFACTION OF GROWTH FACTORS
 The mode of action of the growth factor is the way the growth factor is meant
to interact with its target receptor.
Endocrine mode of action
 The endocrine mode of action is depicted by hormones (contrary to the
growth factors) whereby they are secreted by one cell type and travel in the
blood stream to a distant target cell to exert their actions. Examples of
hormones having this type of action are parathyroid hormone, growth
hormone, and luteinizing hormone.
 Local modes of action are more traditionally associated with the term growth
factor and involve paracrine, autocrine, juxtacrine, and intracrine modes.

15. It involves the production of the factor by one cell secreted in soluble form
outside the cell and then binding to surface receptors on the same cell to evoke
an effect.
e.g., TGF-α which is produced by and acts on epithelial cells, BMPs which are
produced by and act on osteoblastic cells
Autocrine mode of action

16. Paracrine mode of action
 The growth factor is secreted by one cell in a soluble manner and binds to
receptors on the target (another) cell to evoke its effects.
 e.g., PDGF and TGF, which are produced by platelets and act on target cells
such as lymphocytes and osteoblasts.

17. It is similar to the paracrine mode except that the factor produced by cell of
origin is cell surface bound and requires cell contact by the target cell to evoke
a response.
e.g., stem cell factor
Juxtacrine mode of action

18.  It is similar to the autocrine mode in which the factor produced by the cell is
not secreted but acts intracellularly to facilitate the effect.
 e.g., parathormone-related protein (PTHrP) in which a portion of the protein
has been shown to translocate to the nucleus to inhibit apoptosis
Intracrine mode of action

19. RECEPTORS FOR VARIOUS GROWTH FACTORS
 Growth factors are natural cell products; they cannot diffuse across a cell
membrane and must act by binding to high affinity cell receptors.
 For a growth factor to exert its effect, its designated receptor must be present
on the cell membrane in sufficient quantity, orientation, and functional
activity to transmit the appropriate stimuli.
 Growth factor receptors can be broadly divided into two categories.
 Cell surface receptors
 Intracellular receptors.
 Cell surface receptors commonly bind to peptide factors that are soluble in
water but not easily transported across the lipophilic cell membrane.

20. Cell surface receptors can be further divided into the following:
G-protein-linked
receptors
• Platelet-derived growth factor
• Parathormone-related protein
Receptor
tyrosine kinases
• Platelet-derived growth factor
• Insulin-like growth factors I and II
• Fibroblast growth factor
Serine threonine
receptor kinases
• Transforming growth factor β
• Bone morphogenetic proteins

21. The intracellular receptors are commonly described for steroids such as.
 Vitamin D3
 Estrogen
 Glucocorticoids.
 Steroid receptors have been seen in both the cytoplasm & the nucleus of the
target cells. Once a cell surface receptor has been bound and activated, a
series of second messengers are responsible for evoking a biologic activity.
 Four main second messengers are as follows: Adenyl cyclase,
Phospholipase C, Tyrosine kinases & serine threonine receptor kinases.
 Protein phosphorylation is a key component of the growth factor activity and
is responsible for mediating changes in cell proliferation and cell
differentiation which are the hallmarks of the growth factor activity.

23. Common features of GFs
• Growth factors are products that are release or activated
when is necessary. This action occurs during the events
such as tissue regeneration or wound healing.
Natural cell
products:
• Except few, growth factors act locally.
Local action:
• Growth the cell membrane, they exert their activity by first
binding to high-affinity cell membrane receptors. The
capacity of cell to respond to growth factors depend on
presence of these factors.
Receptor
activity:
Regulation:
Multifunctional
activity:
Mechanism of
action:
• The production factors is tightly regulated in normal
• Polypeptide growth factors stimulate wide variety of
cellular activities, which include growth, migration,
differentiation and production of extracellular matrix.
• In some cases, GFs can stimulate the same cell that
synthesizes the molecule (autocrine stimulation) or can
affect nearby cells (paracrine stimulation)

24. Platelet-Derived Growth Factor (PDGF)
PDGF was originally purified from human platelets.
PDGF has been found to be produced by various other cells, monocytes,
megakaryocytes, vascular endothelium, smooth muscles cells, and
transformed cells (Ross et al., 1986; Raines et al., 1990).
PDGF contain two polypeptide chains forming three isoforms either as a
homodimer (AA or BB) or as a heterodimer (AB).
PDGF A and B chains are present in gingival epithelium with PDGF-A
playing an important role during early stages of wound healing while
PDGF-B appears later (Green et al., 1997).
The biologic effects of PDGF are mainly initiated via two tyrosine kinase
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 complex
pattern in healing events (Parker et al., 2001).

25. Actions
of
PDGF PDGF is a chemoattractant for fibroblasts, leukocytes
and smooth muscle cells. It acts synergistically with
IGF-I, promoting protein synthesis and production of
ECM.
It has mitrogenic effects on osteogenic cells, promoting
their proliferation and migration in the healing area,
promotes synthesis of fibronectin and collagen type I, III
and V & inhibits collagenase and plasminogen activator.
PDGF upregulates the expression of angiogenic
molecule like vascular endothelial growth factor
(VEGF) and hepatocyte growth factor, and also the
proinflammatory cytokine interleukin-6, thereby
indirectly promoting periodontal regeneration.

26. Piche et al (1989) demonstrated that PDGF stimulates the proliferation of
cells from the periodontal ligament and the growth is dependent on the
phenotype of the periodontal ligament cells, osteoblastic phenotypes
proliferate much more than fibroblastic phenotypes.
Matsuda et al (1992) reported also that PDGF has a mitogenic effect on
periodontal ligament fibroblastic cells. These cells show a strong chemotactic
response to PDGF. PDGF-AB stimulates collagen synthesis and PDGF-BB
stimulates proliferation and chemotaxis.
Oates et al (1993) also demonstrated that PDGF-AA and-BB are major
mitogens for human periodontal ligament cells.
Dennison et al (1994) found that PDGF stimulates the proliferation from
periodontal ligament cells than from gingival fibroblasts.
Lynch et al. (1991) treated 13 dogs with human recombinant (rh) PDGF-BB
and IGF-I in methyl cellulose gel. Five weeks after surgery, histological
analysis demonstrated a significant increase in new bone and cementum
formation in the growth factor treated sites over that in control sites
Literature review:

27. Mc Allister et al (1995) showed that the proliferative
responses of PDGF-BB are inhibited by bradikinin in cells of
the peridontium.
Park et al. (1995) conducted a study Guided tissue
regeneration around experimentally created horizontal class
III furcation defects with and without the use of PDGF-BB
(solution) in 6 beagle dogs was studied. The authors found
that after 8 to 11 weeks there was statistically a greater
amount of bone and periodontal ligament formed in the
lesions where PDGF-BB was used in combination with GTR.
Nevins et al (2005) conducted a large-scale,
prospective, blinded, and randomized controlled clinical
trial study and demonstrated that the use of rhPDGF-BB +
β-TCP was safe and effective in the treatment of
periodontal osseous defects.

31. Transforming Growth Factor (TGF)
 The TGFs are a family of structurally and functionally unrelated proteins
that have been isolated from normal and neoplastic tissues.
 The two best characterized polypeptides from this group of growth factors are
TGF-α and TGF-β.
TGF-α is a 50-aminoacid single-chain protein
with a molecular weight of approximately 5600
Da
It belongs to the epidermal growth factor (EGF)
family of cytokines. It is a mitogenic polypeptide
and secreted protein, which is expressed by
monocytes, keratinocytes, and variou, tumor
cells
EGF and TGF-α are equipotent at inducing in
vitro endothelial cell proliferation and bind
equally to endothelial cell EGF receptor.
It acts synergistically with TGF-ᵦ to stimulate
anchorage independent cell proliferation and
produce a mitogenic response.

32. TGF-ᵦ
multifunctional
structurally
related growth and
differentiation
factors associated
to the
inflammatory
response.
play an important
role in apoptosis,
angiogenesis,
wound healing
and fibrosis.
TGF-ᵦ is encoded
by three different
genes TGF-ᵦ1,
TGF-ᵦ2 and TGF-ᵦ3
,
It is secreted in an
inactive form and
is activated by
proteolysis and
low pH, which are
present during
wound healing.
It is found in
highest
concentrations in
bone and platelets.
dimeric
polypeptide with a
molecular weight
of 25,000 Da and
consists of 2
amino acid chains
linked together by
disulfide bonds.

33. • PDGF, EGF, FGF
MODULATE
• epithelial cell proliferation
INHIBITS
• extracellular matrix production.
INDUCES
• Fibroblast chemotaxis and
proliferation
STIMULATES
• osteoblast proliferation.
stimulatory and
inhibitory effects
Actions of TGF

34. Matsuda et al (1992) saw that TGF-induces inhibitory effects on mitogenic responses of
the periodontal ligament cells. It reveals no chemotactic effect on these cells, however TGF-
stimulates the collagen synthesis.
Oates et al (1993) compared the mitogenic activity of TGF- with interleukin-1 and
PDGF in fibroblast cells derived from the periodontal ligament, and saw that TGF-
is a weak mitogen compared to PDGF. They supported a role for TGF- as a regulator
of the mitogenic response to PDGF.
Dennison et al (1994) showed that TGF- and PDGF show a significantly greater
increase in proliferation of periodontal ligament cells than in gingival fibroblasts.
Selvig et al. (1994) studied the effects of topical application of a combination of IGF-II, b-
FGF and TGF- ß in a collagen sponge to treat experimentally created fenestration defects in
4 beagle dogs. Histometric analysis showed no differences in fibroblast and collagen density
between control and growth factor defects up to 14 days after surgery. Bone regeneration
was significantly greater in control than in growth factor defects.

35. Bone Morphogenetic Proteins (BMPs)
 The name BMP was given in 1965 by Urist.
 BMPs are a group of regulatory glycoproteins that are members of the TGF-β
superfamily.
 They help in numerous cellular functions including development,
morphogenesis, cell proliferation, apoptosis and ECM synthesis.
 The main action of BMPs is to commit undifferentiated pluripotent cells to
differentiate into cartilage and bone forming cells (Ripamonti and Reddi,
1994; Wozney,1992).
 More than 20 BMP-related proteins have been identified, several of which
induce bone formation.

36.  They act as mitogens on undifferented mesenchymal cells and osteoblast
precursor.
 BMPs induce bone formation, whereas other growth factors such as TGF-ᵦ 1
and PDGF do not.
 BMPs have an anabolic effect on periodontal tissue through the stimulation
of osteoblastic differentiation in human periodontal ligament (PDL) cells
(Eickholz et al., 2007).
 BMP 2-12 singly initate de novo endochondral bone formation (Celeste et
al., 1990; Urist, 1965).
 They induce the expression of osteoblast phenotype (i.e. increase in alkaline
phosphatase activity in bone cells).
 Act as chemoattractants for mesenchymal cells and monocytes as well as
bind to extracellular matrix collagen type-IV (Paralkar et al., 1990).
Properties of BMPs

37. Role of BMPs in periodontal regeneration
• Bowers et al. (1991) found that while osteogenin (BMP-3) augments new bone and cementum
deposition around submerged teeth, it does not significantly enhance new bone or cementum
formation around non-submerged teeth. Using demineralized freeze-dried bone or allografts,
some better results have been reported.
• Sigurdsson et al., (1995) and Kinoshita et al., (1997) successfully achieved periodontal
regeneration in dogs using rhBMP-2 and a systemic carrier.
• Clinical trials using rhBMP-2 in an absorbable collagen sponge carrier (Howell et al., 1997;
Cochran et al., 2000) have yielded encouraging results with the protein and the carrier well
tolerated, locally and systemically
• Cochran LD et al(1999) studied the effects of rhBMP-2 on stimulation of bone formation
around endosseous dental implants. It was demonstrated that a bone differentiation factor
significantly stimulates bone formation in peri-implant bone defect in canine mandible. The
results also demonstrated that rhBMP-2 can be used to stimulate bone growth both around and
onto the surface of endosseous dental implants placed in sites with extended peri-implant
osseous defects.

42. Fibroblast Growth Factors (FGF)
 These are family of structurally related strongly heparin binding peptides
that have been implicated in healing and regeneration.
• FGF-1 has an isoelectric range of 5.6-6.0 and a molecular
weight of approximately 15,000 Da.
• This protein functions as a modifier of endothelial cell
migration and proliferation, as well as angiogenic factor.
• FGF-1 is considered to function in several important
physiological and pathological processes, such as
embryonic development, morphogenesis, angiogenesis and
wound healing
Fibroblast growth factor-1
(FGF-1)/acidic FGF (a FGF)
• FGF-2 has an isoelectric point of approximately 9.6 and
has a molecular weight in the range of 16,000-18,000 Da.
• It has low molecular weight (LMW) and high molecular
weight (HMW) isoforms.
• LMW FGF-2 is primarily cytoplasmic and functions in an
autocrine manner, whereas HMW FGF-2 is nuclear and
exert activities through intracrine mechanism (Arese et al.,
1999).
Fibroblast growth factor-2
(FGF-2)/ basic FGF (b FGF)

43. Action of FGF
a.At
cellular
level
A competence growth factor is the one which stimulate resting cells in G0 phase to enter the cell
cycle in G1 phase.
It is found in association with the ECM in the basement membranes and is attached to hepran
sulphate, which provide protection from degradation and allows it to maintain it biological
potential.
During
wound
healing
The FGF-1, FGF-2 and keratronocyte growth factor (KGF) are primary FGFs involved in wound
healing.
They stimulate proliferation of most of the major cell type involved in wound healing including
vascular endothelial cells, fibroblasts, keratinocyte and chondrocytes.
Angiogenes
is
FGF-2 has ability to induce all steps necessary for new blood vessel formation both in vivo and in
vitro. It regulates the production of collagen type-I and laminin by PDL cells.
FGF-1 stimulates endothelial cell proliferation which enhances new blood vessel proliferation in
healing area.
Effect on
PDL cell
They have chemotactic and mitogenic effects on PDL cells.
Due to overall effects, they play vital role in periodontal regeneration.

44. Terranova et al (1989) demonstrated that b-FGF stimulates human endothelial and periodontal
ligament cell migration and proliferation, and that the combination with an attachment protein,
fibronectin, further enhances periodontal ligament cell chemotaxis.
Takayama et al (2001) The gelatinous carrier alone or the carrier containing 0.1 or 0.4%
human recombinant FGF-2 was topically applied to the defects and compared with no
treatment. Eight weeks after application, the periodontal regeneration in those defects was
analyzed. In all FGF-2-treated sites, significant periodontal regeneration was dose-
dependently observed in greater amounts than in the carrier treated or non-treated
sites.(beagle dogs).
Murakami et al (2003) study- beagle dogs in furcation defects . Twelve furcation class II bone
defects were surgically created in six beagle dogs, then recombinant bFGF (30 lg/site) +
gelatinous carrier was topically applied to the bony defects. Six weeks after application,
periodontal regeneration was analyzed. Topical application of bFGF can enhance considerable
periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.
Tamura et al (2018) conducted a study on periodontal regeneration using gelatin hydrogels
incorporating basic fibroblast growth factor in intra bony defects and concluded that topical
application of bFGF/gelatin hydrogel may promote periodontal regeneration in cases of chronic
periodontitis with infrabony defects.

46. Insulin-like growth factors (IGFs)
 IGFs are first described in 1957 by Salmon and Daughaday (Salmon et al.,
1957).
 They are family of mitogenic proteins that control growth, differentiation and
maintenance of differentiated function, in numerous tissues.
 The IGF family include three ligands (insulin, IGF-I and IGF-II), their
corresponding cell surface receptors (IR, IGF-IR, and IGF-IIR), and atleast six
IGFbinding proteins (IGFBPs).
 It is mainly produced by liver, smooth muscle and placenta , and are carried
in plasma as complex with a specific binding protein.

47. Insulin-like growth
factor-I (IGF-I)
IGF-I is a 70-amino acid
protein with a molecular
weight of 7649 Da and
anisoelectric point of
8.4
It has endocrine,
paracrine and autocrine
effect
It is mainly produced by
liver but virtually every
tissue is able to secrete
IGF-I for
autocrine/paracrine
purposes.
Insulin-like growth
factor-II (IGF-II)
IGF-II[also known as
multiplication
stimulating activity
(MSA)] is a 67- amino
acid neutral peptide
with a molecular weight
of 7471 Da.
IGF-II binds to IGF-II
receptor (IGF-IIR),to
IGF-IR and weakly to
insulin receptor.
. The effect of IGF-II on
metabolism of gingival
fibroblasts is still
uncertain.

48. • Play important role in fetal growth and differentiation.
• IGF-I plays important role in T-lymphocytes development and
function. It can increases the number of CD4+ CD8+ immature T-
cells, promotes T-cells survival proliferation, chemotaxis and
maturation (Tu et al., 2000).
Growthanddevelopment
• It is powerful chemoattractant of fibroblasts and it lead to
periodontal regeneration by stimulating the formation of
mesenchymal tissues including collagen, bone and cementum
(Skottner et al., 1989).
• It upregulates cementoblast mitogenesis, phenotypic gene
expression, and mineralization (Saygin et al., 2007).
Effect at cellular level
• IGF-I is an important factor involved during wound healing
because it is mitogenic for keratinocytes and a potent
chemotactic agent for vascular endothelial cells. Its levels are
increased at healing sites suggesting that its presence is requires
for adequate wound healing(Werner and Grose, 2003).
Role in wound healing
Effect on periodontal ligament cells
Actions of IGF-I
• One study demonstrated the mitogenic effects of IGF-I on
PDL fibroblastic cells and concluded that a synergistic
effect result from using a combination of PDGF-AB and
IGF-I.

49. Blom et al (1992) demonstrated that IGF-I has a mitogenic
effect on fibroblasts originating from various connective
tissues and cell lines, and that IGF-I can stimulate the DNA
synthesis of periodontal ligament fibroblasts.
Matsuda et al (1992) demonstrated that IGF-I has mitogenic
effects on periodontal ligament fibroblastic cells. They showed
that a synergistic effect results from using a combination of
PDGF-AB and IGF-I. IGF-I is chemoattractive to periodontal
ligament cells.
Rutherford et al (1992) also demonstrated that PDGF acts
synergistically with IGF-I to synthesize DNA in periodontal
ligament cells, and found that the corticosteroid
dexamethasone has the same effect as on PDGF.
Cho et al (1994) showed that IGF-I has the ability to induce
premature differentiation of periodontal ligament cells into
osteoblasts and cementoblasts after its application to lesions
and this could lead to ankylosis. IGF-I may be useful for
promoting cementogenesis and or osteogenisis.

50. EGF
The EGF is a
multifunctional
cytokine involved in a
variety of functions,
including epithelial
growth and
differentiation, and
wound healing.
In 1986, Stanley Cohen1
received the Nobel for his
work elucidating the role of
the EGF in the regulation of
cell growth and development.
The major sources of EGF are
urine and salivary glands,
although it also has been
isolated from Brunner's
glands and platelets as well
as from cerebrospinal and
amniotic fluids.
EGF stimulates DNA
synthesis and cell growth in
a large variety of cells,
including those of
epithelial, endothelial and
mesodermal origin.
However, EGF stimulates
prostaglandin production
and induces bone
resorption in cultures of
neonatal mouse calvaria.
It is found in membrane
associated and soluble
form. Both soluble and
membrane associated forms
of EGF are active. Its actions
are activated with its
attachment to epidermal
growth factor receptor (EGF-
R). The EGF-R has 3 major
regions:
1.Extracellular domain which
contains growth factor.
Hydrophobic transmembrane
domain. Cytoplasmic domain
which contains tyrosine
specific protein kinase
Epidermal growth factor (EGF)

52. Vascular endothelial growth factor (VEGF)
 VEGF is a potent angiogenic factor and was first described as an essential
growth factor for vascular endothelial cells. It is also known as vascular
permeability factor (VPF). Originally, it was described as endothelial cell-
specific mitogen.
Sources:
Macrophages, Platelets, Keratinocytes & Tumorcells.
 VEGF is an important growth factor involved in functions such as bone
formation , hematopoiesis , wound healing, and development.
 The VEGF family comprises seven members: VEGF-A, VEGF-B, VEGF-C,
VEGF-D, VEGF-E, VEGF-F, and PIGF (placenta growth factor). All members
have a common VEGF homology domain.

53. Actions:
1. VEGF-A induces angiogenesis by following mechanisms,
2. VEGF-A is chemotactic for macrophages and granulocytes.
3. VEGF-A is involved in vasodilation (indirectly by NO release).
4. VEGF-B is involved in embryonic angiogenesis.
5. VEGF-D is needed for the development of lymphatic vasculature.
6. PIGF is important for vasculogenesis
a. increased migration of endothelial cells.
b. increased mitosis of endothelial cells.
c. increased matrix metalloproteinase activity.
d. creation of blood vessel lumen.
e. creates fenestrations.

54. • Johnson RB et al 1999 speculated that VEGF may be an important factor
in the progression of gingivitis to periodontitis through its role in promoting
the expansion of the vascular network observed in inflammation.
• Pelin Guneri et al (2004) compared VEGF expression in healthy and
periodontally diseased tissues with GCF of healthy and diabetic patients.
• Their study suggested that GCF -VEGF values increased in periodontal sites
of all test groups (DM).

55.  Regeneration of the periodontal tissues is a dynamic process
involving cell-to-cell and cell–extracellular matrix interactions.
 Growth factors elegantly co-ordinate these interactions resulting in
wound healing and regeneration of tissues.
 Combinations of PDGF and IGF have been considered attractive
candidates for regenerative therapies.
 With the advent of the recombinant technique it is now possible to
provide large quantities of purified growth factors for use in invivo
studies.
CONCLUSION

56. REFERENCES
 Carranza 9th Edition.
 Pathologic basis of disease: Robbins & Cotrans 7th Edn
 Biologic mediators of periodontal regeneration Perio 2000;1999:40-59
 Biology of periodontal connective tissues: Sampath Narayanan & Mark
Bartold
 Growth substances: Potential use in periodontics: Western society of
Periodontology Vol:37;3,1989.
 Bone Morphogenetic proteins: Background & implications for oral
reconstruction: A review J Clin Periodontol 1997: 24; 355-365.
 Dabra S, Singh P. A remarkable role of growth factors in resolving oral and
specific periodontal pathologies: A strategic review. Indian J Dent Res
2011;22:496-7.

57. • Divyanshu Jamwal, Pramod Waghmare, Amit Chaudhari, Nilima Landge and
Ketaki KanadeA review”, International Journal of Current Research. 10, (09),
73439-73444.
• Agarwal A, Singh N, Khan M, Nabi Khan SS, Sahu K, Jadhav SU. Role of
growth factors in bone regeneration. Int J Prev Clin Dent Res 2020;7:69-71.
• Mani R., Mahantesha S., Nandini T.K., Lavanya R. Growth Factors in
Periodontal Regeneration. Journal of Advanced Oral Research / May-Aug
2014 / Vol. 5 No. 2.
• Sidhu J et al. Growth factors in Periodontics. Journal of Advanced Medical
and Dental Sciences Research |Vol. 4|Issue 2| March - April 2016.
• Raja S, Byakod G, Pudakalkatti P. Growth factors in periodontal
regeneration. International journal of dental hygiene. 2009 May;7(2):82-9.
• Cochran DL, Wozney JM. Biological mediators for periodontal regeneration.
Periodontology 2000. 1999 Feb;19(1):40-58.

58.  Li F, Yu F, Xu X, Li C, Huang D, Zhou X, Ye L, Zheng L. Evaluation of
recombinant human FGF-2 and PDGF-BB in periodontal regeneration: a
systematic review and meta-analysis. Scientific reports. 2017 Mar 6;7(1):65.
 Vandana KL, Singh G, Prakash S, Bhushan KS, Mahajan N. Periodontal
regeneration by application of recombinant human bone morphogenetic
protein-2 in human periodontal intraosseous defects: A randomized
controlled trial. Int J Oral Health Sci 2016;6:11-7.
 Cochran DL, Wozney JM. Biological mediators for periodontal regeneration.
Periodontology 2000. 1999 Feb;19(1):40-58.
 Murakami S. Periodontal tissue regeneration by signaling molecule (s): what
role does basic fibroblast growth factor (FGF‐2) have in periodontal therapy?.
Periodontology 2000. 2011 Jun;56(1):188-208.
 Bosshardt DD, Sculean A. Does periodontal tissue Regeneration really work?
Periodontol 2000 2009; 51: 208–219.
 Mac Neil RL, Somerman MJ. Development and regeneration of the
periodontium: parallels and contrasts. Periodontol 2000 1999; 19: 8-20.

59.  Caffesse RG, Quinones CR. Polypeptide growth factors and attachment
proteins in periodontal wound healing and regeneration. Periodontol 2000
1993; 1: 69-79.
 Cochran DL, Wozney JM. Biological mediators for periodontal regeneration.
Periodontol 2000 1999; 19: 40-58.
 Bartold PM, Narayan AS. Biology of the periodontal connective tissue. 1st ed;
Quintessence publishing; USA; 1998: 241-266.
 Lindhe J, Lang NP, Karring T. Clinical Periodontology and Implant Dentistry,
5th ed; Blackwell Munksgard; Oxford; 2008:541-562.
 Moore YR, Dickinson DP, Wikesjo UME. Growth/differentiation factor-5: a
candidate therapeutic agent for periodontal regeneration? A review of pre-
clinical data. J Clin Periodontol 2010; 37: 288–298.
 Nevins M, Hanratty J, Lynch SE. clinical results using rhPDGF and
mineralized FDBA in periodontal defects. Int J Periodontics Restorative Dent
2007; 27: 421-427.

60.  Rastogi P, Saini H, Singhal R, Dixit J. Periodontal regeneration in deep
intrabony periodontal defect using hydroxyapatite particles with platelet rich
fibrin membrane–a case report. J Oral Biol Craniofacial Res 2011; 1: 41-43.
 Christgau M, Moder D, Hiller KA, Dada A, Schmitz G, Schmalz G. Growth
factors and cytokines in autologous platelet concentrate and their correlation
to periodontal regeneration outcomes. J Clin Periodontol 2006; 33: 837–845.
 Growth factors. AAP Literature reviews 1999: 189-194.
 Raja S, Byakod G, Pudakalkatti P. Growth factors in periodontal
regeneration. Int J Dent Hygiene 2009; 7: 82–89.
 Matsuda N, Lin W-L, Kumar MI, Genco RJ. Mitogenic, chemotactic and
synthetic responses of rat periodontal ligament cells to polypeptide growth
factors invitro. J Periodontol 1992;63:515-525.
 Okuda K, Kawase T, Momose M, Murata M, Saito Y, Suzuki H et al. Platelet-
rich plasma contains high levels of platelet-derived growth factor and
transforming growth factor-beta and modulates the proliferation of
periodontally related cells in vitro. J Periodontol 2003; 74: 849-857.