collagen

introduction

Collagen is the most abundant protein in mammals, comprising

approximately one-third of the total body protein.
Collagen is the predominant component of the connective tissue,
although its distribution varies in different tissues.
it is the main fibrous component of the skin ,bone , cartilage ,tendon and
periodontium.
The predominant extracellular matrix component of the periodontium is
collagen, a genetically distinct superfamily 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.

Structure of collagen
Triple helical structure.

The collagen molecule consists of 3 distinct polypeptide chains, twisted

around each other to form rod like structure. alpha chains, that form
homotrimeric or heterotrimeric domains.
Depending upon type of collagen the molecule may be made up of either
3identical alpha chains or 2or3 different alpha chains.
Alpha chain-left handed helices that wrap around each other into a right
handed rope like triple helicle rod.
Each such helix is around 1.4 nm in diameter and 300nm in length.

Formation of the triple helix depends on the amino acid composition of the
protein and the winding of the polypeptide chains.
The amino acid sequence of the triple helix is glycine-X-Y, where X and Y
represent the proline and hydroxyproline 30% of the time.
1/3rd of the amino acids are glycine. i.e every 3 rd amino acid is glycine.
 The imino acids rigid, cyclic backbone stabilizes the triple helix by limiting
the rotation
The triple helical structure is stabilized by extensive network of hydrogen
bonds, covalent cross links, electrostatic and hydrophobic interactions and
van der waales forces.
The triple helix domain serves two important functions. It physically
separates the globular domains within the molecule and offers the
potential for lateral interactions from those amino acids in the X-Y
positions.
Types of collagen with respective genes and tissues

The family of collagens can be separated into 7 broad groups:

1) fibrillar,

2) fibril-associated collagens with interrupted triple helices

3)sheet-forming

4) beaded filaments
 5) anchoring fibrils

6) growth plate-specific and

7) miscellaneous.

Fibrillar collagen
Most commonly occuring collagen proteins and accounts for greatest
percentage of mass in all conn.tissues
Forms extensive linear aggregats.

Fibril formation is is an exact ,parallelconfiguration of collagen molecules is

a letral association of collagen molecules staggered by 67nm.
It includes collagen type I,Type II, Type III,Type v, type XI.

Fibril associated collagens with interrupted triple helices (FACITs)

They do not form fibrills .

Consist of interrupted triple helices and large amino terminal domains.

3 functional domains

One domain consist 1-2 of triple helices, interacts and adheres to fibrils

Second domain also consist triple helix, which projects out of the fibril.

Third domain which consist of a non helical ,globular region is thought to

be involved with matrix or cellular interactions.
 it has been suggested that fibril associated collagen with interrupted triple
helical structure connects fibrillar collagen to matrix.
It includes type IX, type XII, type XIV collagens

Collagen forming sheets

Non fibrillar collagen, have regions of helical and non helical structure
domain.
Unable to associate into compact banded fibers.

Type IV Forms a complex ,branching ,net like structure whose globular

regions contact with other type4 molecules.
These collagens found in basement membranes.

Type VIII-Dumbbell shaped molecule-forms hexagonal lattices.

Collagen forming beaded filamentsOnly type VI collagen is included in this

class.
Heterotrimrtric molecule consist of short triple helix domain with large
nonhelical amino and carboxyl regions.
Function of type VI is not known
 Pathologic accumaltions have been noted in sevral fibrotic diseases and
osteoarthritic disorders.

Collagen forming anchoring fibers

Type VII.

Homotrimrtric molecules that contains very large globular region.

The cell type secreting type VII collagen is keratinocytes.

Forms an association with type IV,in basement membrane and the

anchoring plaques in conn. Tissues.
secure basement membrane to underlying stroma.

Ulterations seen in disease like epidermolysis bullosa.

Growth plate specific collagens

Homotrimetric collagen .

Type X structural homology to type VII,but not shown to produce a sheet

structure.
Secreted by hepertrophic chondrocytes

Associated with endocondral bone formayion.

Function is not known

Suggested that it might influence the remodelling of cartillage prior to

calcification .

Miscellaneous collagen
Type XII

No well define function and stochiometry.

Alpha chains consist of 3 collgenous and 4 noncollagenous domains.

Collagen in periodontium and tooth structure
gingival
In healthy gingiva,collagens accounts approximately three fifth of total
protein.
Collagen type I forms the bulk of lamina propia and provides the tensile
strength to the gingival tissue.
Type I and Type III has less proline and hydroxyproline and more lysine and
hydrolysine than skin type I collagen
Type IV-(Argyrophilic Reticulum Fiber) is locted on basement membrane.

Periodontal ligament
Main type of collagen in pdl is type I and type III

Type I accounts for more then 70% of pdl collgen

Uniformly distributed in pdl with two identical 1and 2chains.

 Reticular fibers are composed of Type III collagen& accounts for about
20% of pdl collagen.
Consist of three identical 1(III) chains.

Type III is linked with type I thruoght the ligament.

Small amount of type V and type VI and traces of type IV and typeVII are
also found in ligament
Type IV is associated with major binded collagen fibers but may play role
in maintaning elasticity and integrity of extracellular matrix,Found in basal
lamina.
Type IV and type VII are associated with epithelial cell rests and blood
vessels.
Type VIII is belived to to occour within pdl ,only when ligament is fully
functional.
Cementum

Organic matrix of cementum is composed of type I (90%) And type

III(about 5%)
Sharpeys fibers which forms the bulk of the cementum are composed
mainly collagen type I .
Collagen type III appears to coat the type type I collagen of shrpeys
fibers.
Alveolar bone

The organic matrix of bone is known as osteiod , and it sis made up of

collagen and noncollagenous proteins.
Collagen is major organic component of mineralised bone tissue

Type I collagen (>95%) is the principal collagen and together with type V
(<5%) ,Forms heterotypic fiber bundles that provide the basic structural
integrity of conn. Tissue.
The elastisity of collagen provides resillency to tissue and help to rsist
fracture .
Also contains type I, Type III,Type v, And type XII collagen

Sharpeys fibers contain type III with type I collagen.

BIOSYNTHESIS OF COLLAGEN

Collagen is a protein composed of amino acids like proline,hydroxylysine

and hydroxyproline.
The biosynthesis of collgen occurs in fibroblasts to form Tropocollagen
molecule Microfibrils
 Fibrils

Fibers

Bundle

Collagen crimping
Diament demonstrated that collagenous tissues exhibit a quantifiable
periodicity of structure of variable scale and this wave for that describes
this periodicity has been referred to
as a crimp.
Fibroblast processes in the developing collagenous tissues play a role in
fabricating the crimpedarrangement and consequently that crimping may be an
important feature in tooth eruption.
In polarizing microscope, crimping can be recognized by a regular
banding of dark lines across a
collagenous bundle observed when its axis lies perpendicula to the
polarizer directions.
 Crimping may be due not only to a sharp
zig-zag arrangement of collagen fibrils, but also to the micro anatomical
organization of collagenous
sheets and bundles.
COLLAGEN TURNOVER IN THE PERIODONTAL
LIGAMENT
Measurements of tritiated proline and glycein uptake in the
periodontal ligament of erupting teeth have indicated that there
is a high turnover of collagen with a half-life varying between 3
and 23 days.
The turnover rate of collagen in the periodontal ligament is
estimated to be several times greater than in skin and oral
mucosa (Sodek).
 Functional adaptation of collagen fibers of the periodontal fibers.
Current theories of tooth support envisage a multiphasic system
involving fibers, ground substances, blood vessels and fluid, all
acting together to resist mechanical forces and it seems that
there is both tension & compression of the tissues.
Minns et al. showed that the internal orientation of collagen fibers
in the connective tissues influences the mechanical properties of
the tissues and suggested that, in general the collagenous
bundles could best resist axially directed forces.
The arrangement of majority of the periodontal ligament collagen
fibers are in horizontal & oblique direction and hence may be
adapted to resist, axial forces.
But the overlapping arrangement of the bundles seen in scanning
electron microscopy & by polarizing microscopy demonstrated
their ability to resist rotational forces.
The overlapping arrangement of the bundles is also advantageous
in resisting intrusive forces.
Degradation of collagenBreakdown of collagen is the normal
component of tissue remodelling
There are two pathways of collagen degradation

i.e intracellular phagocytosis

extracellular mmps

Intracellular ( phagocytosis) Collagen is phagocytosized by

fibroblasts.
Electron-lucent zone

Electron dence zone

Phagosome fuses with pri.lysosme phagolysosome

Electron dense zone suggesting that enzyme degradation has

occur and fibril loses its chractristic structure.
Extracellular eventsRapid degradation of collagen by activity of
enzyme called as collagenase.
Extracellular involves collagenase(MMP-1)

Triple helical portion of molecules within the fibril .

together with MMP-IV denaturation of collagen under

physiologic condition.
 Rest molecules undergo proteolysis by MMP-II(gelatinase),MMP-
IV.
Age changes in periodontal collagen fibers

The main changes that occur with age is increased collagen

fibrosis and decreased cellularity (Grant and Bernick).
The fiber bundles were thicker and that the fiber groups were
broader and more highly organized with areas of hyalinization and
decreased argyrophlia increased
fuschinophilia and a reduction in alcian blue-positive areas.

Decrease in the number of periodontal fibers with increase in size

of interstitial spaces.
Severson et al found that the periodontal alveolar bone surface
was smooth and regular in young adults but in older adults the
corresponding surfaces were jagged and uneven and an irregular
insertion of the fibers was seen.
Cementum was thicker in aged tissues and the cementum surface
also became irregular with time.
This irregularity of the fiber insertion together with replacement
of some of the periodontal ligament space by interstitial areas
and fat cells suggests that the structural organization of the
periodontal ligament degenerates with age