2. CONTENTS…
a. Introduction
b. Structure/Chemical Comp. of collagen
c. Type of collagen
d. Synthesis of collagen
e. Collagen in periodontium
f. Functional adaptation of collagen in periodontium
g. Degradation and remodelling
h. Diseases of collagen related to periodontium
i. Conclusion
3. INTRODUCTION
Collagen is a family of highly developed fibrous proteins found in all
multicellular animals. It is the most abundant proteins found in
mammals, constituting 25 percent of the total protein mass.
Collagen is the main fibrous component of skin, bone ,tendon,
cartilage and periodontium.
It comprises about 90% of the organic matrix of the bone. Collagen is a
natural protein that provides our bodies with structural support.
4. Today, the intercellular substance of tissue, or the extracellular
matrix, is recognized as a complex, interactive compilation of
proteins in dynamic equilibrium that can regulate the gene
expression of cells.
The predominant extracellular matrix component of the
periodontium is collagen, a genetically distinct super family of
extracellular macromolecules that contain one or more triple-
helical domains. There are as many as 25 different genes that
code for at least 14 different collagen molecules
Six different collagen types have been detected in the
periodontium
6. Therefore this protein is an important structural component in
tissues such as the
periodontal ligament and muscle tendons
in which the mechanical forces need to be transmitted
7.
8. All collagens are composed of 3 polypeptide
alpha chains coiled around each other to form
the tripe helix configuration. The individual
polypeptide chains of collagen each contain
app. 1000 amino acid residues .
9. An alpha-triple helix of collagen is shaped into a right handed helix. The Alpha chains
each are shaped into a left-handed symmetry (i.e. the opposite way round), and then
three of these coiled strands get together and form a right-handed triple helix of
collagen.
Depending upon the type of the collagen , the molecule may be made up of either 3
identical Alpha chains(homotrimers), or two or three different alpha
chains(heterotrimers).
ALPHA HELIX OF COLLAGEN
10. Each such helix is around 1.4 nanometers in diameter and 300 nanometers in length
The triple helix may be of continuous stretch or interrupted by non collagenous elements
12. Proline helps in the formation of helical orientation of each alpha chain
Glycine The smallest amino acid found in every 3rd position in the polypeptide chain
-GLY-X-Y------------------GLY-X-Y-
X-Proline
Y- Hydroxy proline
Hydroxy lysine
13. Proline frequently occupies the X position.
Hydroxyproline and hydroxylysine are two unique amino acids.
Vertebrate collagens exhibit the two of them in the Y positions
Each collagen molecule is stabilized through lysine derived intra and
intermolecular cross links.
Each α chain comprises of around 1056 amino acids.
There are around 3 amino acids per turn
14. HYDROXYPROLINE AND HYDROXYLYSINE
Extra Capacity for Hydrogen Bonding. Prevents denaturation of collagen fibers in temperature
changes. Non hydroxylated triple helices have been shown to undergo denaturation at
temperatures below 37*C.
15. 19 different collagen types have been discribed so far.....
Many genetically, chemically, and immunologically distinct types of collagen have been
identified.
16. Variations are due to….
Differences in the assembly of basic polypeptide chains
Different lengths of the helix
Various interruptions in the helix and
Differences in the terminations of the helical domains
17.
18. Collagens are divided roughly into 3 groups based on
their abilities to form fibrils. They are as follows….
1.Fibrils forming protein
Form banded fibrils
Type I
Type II
Type III
Type V
Type XI
19. 2.Fibril associated collagens with interrupted triple helices
( FACIT )
This group of collagens consists of proteins in which collagenous domains are
interrupted by non collagenous sequences. These are associated with the surface of
fibril forming collagens.
Includes type IX, type XII, type XIV and perhaps type XVI also. The former three are
unique in containing glycosaminoglycan components covalently linked to the protein
molecule.
20. 3)All other non fibrillar collagens form the third group
which includes
Type IV, type VIII and type X ( network forming collagens)
Type VI ( beaded fibril forming collagen)
Type VII ( anchoring fibrils and invertebrate cuticle collagen)
In addition to the above collagen groups at least 10 non collagenous proteins incorporating
short triple helical collagen domains have been described
21. 4)This group of collagen domain containing non matrix
protein molecules includes (10 Non Collagenous Proteins)
C1q component of C1 complement
Lung surfactant protein
Acetylcholine esterase
Conglutinin
Mannose binding protein
These proteins are not considered true collagens because they do not form a part of the
extracellular matrix.
22. COLLAGEN IN PERIODONTIUM AND
TOOTH STRUTURES
COLLAGEN IN PERIODONTIUM
The collagen of PDL is largely Type I , with lesser amounts of type III , IV , VI and XII .
Collagen fibers of the periodontium ( particularly Type I ) provide the structural requirements to
withstand intrusive forces of mastication ( tooth support ) and also to accommodate growing
tooth in mammals.
23.
24. DENTIN COLLAGEN
It has been found that type I collagen with the
structure [α1 (I) α2 (I) ] was the most exclusive
collagen in dentine and predentine
Demineralized dentine and predentine show closely
packed collagen fibers of 20-50nm
Dentinal collagen contains 2-3 fold increase of
hydroxylysine compared to that of soft tissues.
Dentinal collagen is relatively insoluble in acid and
neutral solutions
The only other collagen synthesized in culture by
odontoblasts is type V collagen which is secreted into
predentine( only 3%).
25. CEMENTAL COLLAGEN
The amino acid composition of human cemental collagen resembles that of type I
collagen.
5% of type III collagen is accounted for the Sharpey’s fibers that are a part of the
periodontal ligament.
Major cross link is dehydrodihydroxylysinonorleucine (DHLNL)
The other cross link is dehydrohydroxylysinonorleucine (HLNL).
26. PULPAL COLLAGEN
Approximately 34% dry weight of pulp is collagen
There is higher content of collagen in the radicular areas compared to the pulp chambers
and higher concentration in the middle and apical portion of the root compared to the
rest of the tooth
After a small increase in collagen synthesis which occurs at the time of eruption and root
closure, there is no change in collagen content of the tooth for rest of the life
27. BONE COLLAGEN
It contains type I collagen predominantly with the molecular configuration of [α1 (I) α2
(I)].
During its formation in the osteoblast the large procollagen precursor undergoes
important post translational modifications. Suitably located proline and lysine residues
are hydroxylated to hydroxyproline and hydroxylysine respectively
The collagen of bone has less diglycosylated hydroxylysine than that of skin.
The ratio of glycosyl-galactosyl hydroxylysine to galactosyl hydroxylysine is 0.47 in bone
compared to 2.06 in skin
28. GINGIVAL COLLAGEN
Collagens are the most abundant biochemical constituents of gingival CT(90%).
The collagen matrix of gingival CT is well organized into fiber bundles, which constitute the
gingival supra alveolar fiber apparatus.
Based on their preferential orientation, architectural arrangement and sites of insertion they
are classified as :
30. PERIODONTAL FIBRES
It contains type I and type III collagen.
Relative proportion of type III to type I
varies from 10-25%
Type III collagen fibers are smaller in
diameter and appear to withstand
deformation better than type I. It also helps
reduce fibril diameter with type I.
Type IV is found in the basement
membranes and type V with cell
surfaces(0.1-0.2%).
Major crosslink is of
dihydroxylysinonorleucine while
hydroxylysinonorleucine is a minor
component
32. SHARPEY FIBRES
Collagen are arranged in bundles and they form the
Principal Fibers . The terminal ends of the collagenous
principal fibers are inserted in to bones to form
Sharpey Fibers.
At their insertion the collagen bundles of PDL are
embed in to cementum and alveolar bone in a manner
similar to tendon inserting in to the bone . They usually
tend to be concentrated in the crestal region.
Some Sharpey fibers pass right through alveolar bone ,
which implies that there may be continuity between
the collagen fibers of the PDL of adjacent teeth . (
Transalveolar Fibers )
Sharpey Fibers are enclosed within a sheath of collagen
Type III and it not only confers elasticity on the fibers
but it also maintains the elasticity of the fibers when
33. ELASTIC FIBERS OF PDL
In PDL the collagen fibers are
associated with elastic mesh
work which may function either
as a static elastic element or as
a resilient material.
The 3 fibrous components are
OXYTALAN , ELAUNIN & ELASTIN.
Oxytalan fibers form a 3D
meshwork that extends from the
cementum to the periodontal
blood vessels. The size of the
fibers vary depending on the
site.
A- CEMENTUM
B- OXYTALAN FIBRES
C- OXYTALAN TRACT
D- PERIODONTAL VESSEL
34. It is oriented in the Apico Occlusal plane .
Oxytalan & Elaunin Fibers are precursors of the elastin fibres.
Oxytalan fibers are composed of microfilaments surrounded by amorphous material.
Elastin fibers are composed of microfibrillar glycoprotein and amorphous elastin.
Elementary units of elastin are Rod-Like in shape .
Elastin fibers are found only in the PDL of some species.
35. BIOSYNTHESIS
Sites For The Synthesis of Collagen :
1.Mesenchymal Cells & Their Derivatives
FIBROBLASTS ( major cells )
Chondrocytes
Osteoblasts
Odon oblasts
Cementoblasts
2.Other Cells : Epithelial cells. Endothelial cells. Muscle cells. Schwann cells.
37. •
The entire process of collagen synthesis can be best understood under the following stages …
Gene Expression
Translational and post translational events or intracellular steps in
collagen synthesis procollagen formation
Extracellular collagen biosynthetic events
extracellular
Regulation of synthesis
38. INTRA NUCLEAR STEPS
The 3 polypeptide chains of collagen molecule are formed
separately under the direction of their respective genes. The
initial RNA transcript is processed to mRNA.
After Nuclear steps the mRNA translocates to cytoplasm where it
binds to ribosome to get translated & codes for PreProCollagen.
CYTOPLASMIC STEPS
Pre Pro collagen Cleavage of Signal Peptide
PROCOLLAGEN α CHAIN Hydroxylation
Glycosylation Association C terminal Peptides Disulphide
Bond Formation PROCOLAGEN MOLECULE Passes in to
golgoi complex combines with Secretory Vacuoles to move
outside cell .
39. EXTRACELLULAR STEP
REMOVAL OF TERMINAL PRO PEPTIDES
Cleavage of C & N Pro peptides by C & N Proteinase .
ASSEMBLY OF COLLAGEN
The collagen molecules then align themselves laterally to each other ,
having a quarter over-lap such that there is typical 64nm banded
appearance. These fibrils are immature and lack strength
CROSS LINK OF FIBRILS TO FORM FIBRES
Cross-linkage is a slow process and the tensile strength of collagen steadily increases over a
long period
40.
41. REGULATION OF COLLAGEN SYNTHESIS
Collagen biosynthesis is tightly regulated during normal development & homeostasis in a cell
& tissue specific manner .
POST TRANSLATIONAL
MODIFICATION
GENE TRANSCRIPTION
42. Tooth support system is a multiphasic system comprising of fibres , ground substances,blood
vessels,fluids acting together to resist mechanical forces.
MECHANICAL FORCES Axially & laterally directed
Tension & Compression
Majority of PDL collagen fibers are arranged in to Horizontal & Oblique directed groups to
adapt to axial forces.
OVERLAPPING ARRANGEMENT This overlapping arrangement is very crucial in withstanding
Rotational & Intrusive Forces
43. Break down of the collagen matrix element is a key component of any normal tissue that is
undergoing morphogenesis and growth. But it is vital that this process is kept under rigid
control.
Collagen Degradation by MMPS Collagen Denatured
Four types of proteolytic enzymes, capable of ECM degradation
Matrix metalloproteinases (MMPs)
Serine proteinases (e.g. plasmin)
Cysteine proteinases (e.g. cathepsin K) and
Aspartic
44. The MMPs are considered to be essential for the degradation
The collagenases are responsible for the first degradation step of collagen
Gelatinases and cysteine proteases further degrade the collagen fragments
COLLAGEN DESTRUCTION IN INFLAMMATION
GINGIVITIS :-
In initial lesion – perivascular loss of collagen can be seen.
In early lesion - increase in the amount of collagen destruction is seen, 70% of collagen is
destroyed around the cellular infiltrate
In established lesion – collagen fibers are destroyed around the infiltrate of intact and disrupted
plasma cells, neutrophils, lymphocytes, monocytes and mast cells.
46. As age advances qualitative and quantitative changes of
collagen are seen
-Higher conversion of soluble to insoluble collagen
-Increased mechanical strength.
- More organized and thicker.
- Areas of hyalinization.
-Increased denaturing temperature
-Apparent decrease in the number of collagen & PDF
fibers due to Increased Fibrosis+ decreased cellularity.
- Gradual decrease in the number of synthesizing
connective tissue cells
- A gradual recession of alveolar bone. Irregular
Alveolar Bone & cementum surface.
These changes are due to higher cross linking and
stabilized forms of collagen
47. COLLAGEN AS BIOMATERIAL IN
PERIODONTICS
Drug delivery- For LDD in periodontal pockets
Tissue augmentation- recession coverage Collagen
membranes are used as an alternative to connective tissue
grafts in mucogingival surgeries
Bone substitute- as bone grafts in intra-bony defects
Collagen has been used as implantable carriers for bone
inducing proteins Collagen itself is used as bone substitutes
due to its osteo-inductive activity.
Osseograft/DMBM is one such de-mineralized bone derived
Type-I collagen for bone void filling applications
48. COLLAGEN DISORDERS
Collagen diseases may be genetic, auto-immune or miscellaneous like defects due to
nutritional deficiencies, drug induced defects etc.
OSTEOGENESIS IMPERFECTA
EHLER-DANLOS SYNDROME
50. CONCLUSION
Mechanisms that regulate collagen synthesis have a direct bearing on periodontal structures in
which the connective tissues specially collagen undergo dynamic changes during periodontitis
and drug-induced gingival hyperplasia
A balanced synthesis , regulation and degradation of collagen ensures a healthy periodontal
health.
Most diseases in higher animals involve collagen containing connective tissue directly/indirectly
51. REFFERANCES
Shrutal Narendra et al.Enigmatic insight into collagen J Oral Maxillofac Pathol. 2016 May-Aug;
20(2): 276–283.
Carranza’s. Clinical Periodontology. 12th ed.New Delhi:Elsevier ;2015. pp. 17, 23-24 ch.-1
Nanci A. Ten Cate's Textbook of Oral Histology, Development, Structure & Function. 7th ed. New
Delhi: Elsevier; 2008. pp. 66–8. Ch. 4
Shafer WG, Hine MK, Levy BM. A Textbook of Oral Pathology. 4th ed. Noida: Elsevier Saunders
Publication; 2009. pp. 109–10.
Neville BW, Damm DD, Allen CM, Bouquot JE. Oral & Maxillofacial Pathology. 2nd ed. Noida:
Elsevier Saunders Publication; 2008. pp. 349–50
52. Stenzel et al. Collagen as a biomaterial. Annu Rev Biophys Bioeng. 1974;3:231–53.
Pintippa et al. Collagen members: A Review. J Periodontol. Feb 2001;72:215-29
