VIVEKANANDHA DENTAL COLLEGE FOR WOMEN

Elayampalayam-637205.Tiruchengode, Namakkal (Dt)

DEPARTMENT OF PERIODONTICS

SEMINAR ON

COLLAGEN

Dr. P.S.Viola Esther

PG student
2015-18
 COLLAGEN
CONTENTS

INTRODUCTION

STRUCTURE OF COLLAGEN

SYNTHESIS OF COLLAGEN

TYPES OF COLLAGEN

COLLAGEN IN PERIODONTIUM AND TOOTH STRUCTURES

DEGRADATION & REMODELLING OF COLLAGEN

ALTERATION OF COLLAGEN IN GINGIVITIS & PERIODONTITIS

AGING OF COLLAGEN

COLLAGEN AS BIOMATERIAL IN PERIODONTICS

DISEASES ASSOCIATED WITH COLLAGEN

CONCLUSION
INTRODUCTION

The word collagen comes from the Greek word,“kola,” meaning, “Glue

producing” Collagen is protein structures distributed throughout the animal

kingdom.

In French the word collagen designates glue producing constituents

because collagenous tissues were used as sources of glue and

gelatin.Collagen constitutes about one third of the total protein in the

body.

Collagen, in the form of elongated fibrils, is mostly found

in fibrous tissues such as tendon, ligament and skin, and is also

abundant in cornea, cartilage, bone, blood vessels, the gut, and

intervertebral disc.

Collagen constitutes one to two percent of muscle tissue, and

accounts for 6% of the weight of muscles. Collagen forms the major

structural component it also alters the cell shape, differentiation and

the activities of extracellular matrix forming an important group of

multifunctional connective tissue protein.

 Collagen is an important component of tissues like periodontal

ligament and tendon where mechanical forces need to be transmitted

without loss.

STRUCTURE OF COLLAGEN

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 contain

approximately 1000 amino acid residues. 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 righthanded triple helix of collagen.

 The triple helix may be a continuous stretch, or interrupted by non collagenous

segments.(Ramachandran&Ramakrishnan,Piez 1976).

Collagen is rich in proline,hydroxyproline and glycine. Glycine occupies every third

position within the repeated amino acid sequence in the triple helical domain.Sequence often

follows the pattern Gly-Pro-X or Gly-X-Hyp.

Glycine is essential because any larger amino acid cannot fit in the center of triple

helix.

Hydroxyproline and Hydroxylysine are unique amino acids .The collagenmolecule is

stabilized by a number of lysine derived intra and inter molecularcrosslinks.

SITES OF COLLAGEN SYNTHESIS

Mesenchymal cells and their derivatives:

 Fibroblasts

 Osteoblasts

 Odontoblasts

 Chondrocytes

 cementoblasts

OTHER CELLS:

 Endothelial cells

 Muscle cells

 Epithelial cells

COLLAGEN BIOSYNTHESIS
collagen

EXTRACELLULAR Aggregation
crosslinking
interaction with matrix molecules

Collagen fibers

(Byers1995;prockop,Kiirikko1995)
REGULATION OF COLLAGEN SYNTHESIS

Mediator Major source Collagen

Synthesis

Growth factors Platelets, smooth muscle cells, macrophages, Increases

PDGF,TGF-β, FGF,IGF matrix

serum, matrix proteins

Cytokines Macrophages, mast cells Lymphocytes Decreases

IL-1α β, IFN-γ, TNF-α Monocytes macrophages

Others Monocytes/macrophages Decreases

PGE2

TYPES OF COLLAGEN

19 different types of collagen have been described by Prockkop and Kivirrikko

1995, van der Rest and Garrone 1991.

They are divided into three groups depending on their ability to form fibrils.

1.Fibril forming collagens.

2.FACIT collagens.

3.Nonfibrillar collagen

1)Fibril forming collagens:

  Type I

 Type II

 Type III

 Type V

 Type XI

2)Facit collagens:

 TYPE IX

 TYPE XII

 TYPE XIV

 TYPE XVI

3)Nonfibrillar collagens

 -Network forming collagens –Types IV, VIII and X.

 -Beaded –Type-VI

 -Anchoring fibrils-Type-VII

 -Cuticle collagens-in invertebrates.

 -These collagens form a sheets or protein membranes that encloses tissues and organs.

TYPE TISSUE DISTRIBUTION MAJOR FUNCTION

Fibril-forming
In skin,bone,dentin, Provides tensile strength
collagen
cementum,tendons ligaments &
Type l
most connective tissue

Type ll Cartilage, intervertebral disc Provides tensile strength

Type lll Embryonic connective tissue, Forms structural framework of

pulp , skin , blood vessels , spleen, liver,lymph nodes,

lymphoid tissue smoothmuscle,adipose tissue.

Provides tensile strength to

connective tissue

Type IV Basement membrane Forms meshwork of the lamina

densa of the basal lamina

Type V Bone,dermis,cornea,placenta Provides tensile strength,

associated with type I collagen,

also with placental ground substance.

Microfibril-forming Ligament, skin, cartilage , placenta Bridging between cells and

collagen matrix (has binding properties

Type VI for cells, proteoglycan, and

type I collagen)

Anchoring-fibril Epithelium (skin, mucosa) Forms anchoring fibrils that

collagen connective tissue fasten lamina densa to

Type VII underlying lamina reticularis

Type VIII Heart,brain,dermis, kidney Tissue support, porous

meshwork, provide

compressive strength

Fibril associated Cartilage , vitreous humor Associates with type II

collagen with collagen fibers

interrupted triple

helices

Type IX

Type X Hypertrophic zone of cartilage Calcium binding

growth plate

Type Xl Cartilage , vitreous humor , Provides tensile strength ,

placenta controls lateral growth of

type ll fibrils

Type Xl Cartilage , vitreous humor , Provides tensile strength ,

placenta controls lateral growth of

type ll fibrils

Type XII Widespread in many connective Modulates fibril interactions

tissue with type l collagen

Transmembrane Epidermis, hair follicle, cell Cell-matrix, cell-cell adhesion

collagens surfaces,endothelial cells

Type XIII

Type XIV Widespread in many connective Modulates fibril interactions

tissue

Multiplexin Epithelial and basement membranes, adrenal Stabilizes skeletal

Type XV gland , pancreas , kidney muscle cells

Type XVI Endothelial , perineural , placenta , cartilage Associates with hetero-

 -typicII/XI/IX fibrils

Type XVII Hemidesmosomes Cell attachment to matrix

Type XVIII Epithelial and basement membranes, liver , Anchors vitreal collagen

lung , kidney fibrils,determining

retinal structure

Type XIX Endothelial , perineural , muscle Muscle differentiation

Type XX Corneal epithelium , skin , cartilage ,tendon, Associates with fibrils

heart , lung liver , kidney , pancreas, spleen.

Type XXI In developing connective tissue , maintain extracellular

abundant in vascular walls matrix integrity

Type XXII Hair follicle , myotendinous Cell adhesion ligand

junction

Type XXIII Heart , retina , metastatic Cell matrix interaction

tumor cells

Type XXIV Bone , cornea Regulation of type l

Fibrillogenesis

Type XXV Neurons Neuron adhesion

 Type XXVI Developing testis & ovary Unknown

Type

XXVII Cartilage , eye , ear , lungs Association with type II

fibril

Type Dermis unknown

XXVIII

COLLAGEN IN PERIODONTIUM AND TOOTH STRUCTURES:

COLLAGEN IN DENTIN:

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.

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.

Type I and type III collagen are found in the pulpal tissue.The former is concentrated around

blood vessels and between odontoblasts whereas the latter appears as fine branched filaments
distributed as network throughout the pulp.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

CEMENTAL COLLAGEN

Organic matrix is primarily collagen. Mostly contains type l also small quantity of type lll,V VI and

XII.The amino acid composition of human cemental collagen resembles that of type I collagen.

Major cross link is dehydrodihydroxy -lysinonorleucine (DHLNL). The other cross link is

dehydrohydroxylysinonorleucine (HLNL).

5% of type III collagen is accounted for the Sharpey’s fibers that are a part of the

periodontal ligament. Sharpey’s fibers constitute bulk of the organic portion of

acellularcementum less in cellular cementum.

COLLAGEN IN GINGIVA

Type I,III,IV,V,VI,VII are found in gingiva. Collagen type l forms bulk of CT and provides

tensile strength to gingival tissue. The collagen matrix of gingival CT is well organized into

fiber bundles , gingival fibers. Gingival fibers brace the marginal gingiva against the tooth,

withstand mastication forces.Based on their preferential orientation, architectural

arrangement and sites of insertion they are classified as :

1.Dentogingival

2.Dentoperiosteal

3.Alveologingival

4.Periosteogingival

5.Circular and semicircular

6.Transgingival

7.Transseptal

8.Interpapillary

9.Intercircular

10.Intergingival
COLLAGEN IN PERIODONTAL LIGAMENT

The predominant collagens of PDL are types I and III.Small amounts of types V,VI

and XII collagens are also found. Molecular configuration of collagen fibers provides them

with a tensile strength.Collagen imparts a unique combination of flexibility and strength to

the tissues.

PRINCIPAL FIBERS OF PERIODONTAL LIGAMENT

 Alveolar crest group

 Horizontal group

 Oblique group

 Apical group

 Interradicular group
COLLAGEN IN ALVEOLAR BONE

Predominantly has type I (90%)& type III collagen. The collagen fibers attached to bone has

- larger diameter

- small in number

- less matured

- rapidturn over than the collagen attached to cementum.

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

diglycosylatedhydroxylysine than that of skin.The ratio of glycosyl-galactosylhydroxylysine

to galactosylhydroxylysine is 0.47 in bone compared to 2.06 in skin

DEGRADATION AND REMODELLING OF COLLAGEN

Extracellular matrix remodeling requires the degradation of its components. In general, four

types of proteolytic enzymes, capable of ECM degradation, exist:

 Matrix metalloproteinases (MMPs)

 Serine proteinases (e.g. plasmin)

 Cysteine proteinases (e.g. cathepsin K) and

 Aspartic proteinases.

EXTRACELLULAR DEGRADATION:

The altered integrity of the extracellular matrix causes increased water to enter the collagen

bundles causing loosening of the bundles thus allowing the cells that secrete degrading MMPS to

enter the bundles.

Collagenases

 Type 1- MMP 1(fibroblast type)

 Type 2 – MMP 8 (neutrophil type)

 Type 3 – MMP 13 (found in breast cancer)

Gelatinases

 A – MMP 2

 B – MMP 9

Stromelysin

 Type 1 – MMP 3

 Type 2 – MMP 10

 Type 3 - MMP 11

Matrilysin

 MMP 7

Membrane type MMP’s

 MMP 14, 15, 16, 17.

Enamelolysins

 MMP 19, 20

REGULATION OF MMP

The destructive property of MMP is kept under control by 3 mechanisms.(Birkedal Hansen

et al 1993)

1st mechanism:

These enzymes are present in tissue as inactive precursors and conversion to an active form

requires activation by plasmin , trypsin or other proteinases. These are activated when the

condition demand and they are also regulated by other proteins such as tissue plasminogen

activator.
2nd mechanism

Through modulation of synthesis, IL-1,TNF-alpha,PGE2 increase MMP production from

both keratinocyte and fibroblasts.TGF-beta also increase MMP production in fibroblasts but

decreases in keratinocytes.in macrophages MMP production is stimulated by LPS,but decreased by

IFN-gamma ,IL-4,IL-10.

3rd mechanism

The activities of MMPs are neutralised by inhibitors present in the serum like TIMP alpha 2

macroglobulin that binds to MMP1 and inhibits MMP1.

INTRACELLULAR DEGRADATION

Fibroblast that are in intimate contact with the fibers

Identify the alterations in the structure of collagen

Cleave the fibrils and phagocytose of fibrils

Forming phagosome then the phagolysosome

Further degraded by the lysosomal enzymes especially cathepsin.

ALTERATION OF COLLAGEN IN INFLAMMATION

In gingivitis tissue destruction begins within the perivascular extracellular matrix where most

of the collagen within the foci of inflammation is degraded.Quantitative and Qualitative

changes occur in gingival collagen in patient with the above disease.

In gingiva collagen becomes more soluble.Type I & II collagen are destroyed at the

foci of inflammation. Type V collagen increases and its amount may exceed that of Type III.

A new collagen species, Type I trimer can be detected in inflamed gingiva

GINGIVAL OVERGROWTH:
Characterized by increased gingival mass associated with fibroepithelial changes and an

accumulation of connective tissue matrix .Type I/III ratio becomes different with loss of type

I and elevated levels of type III collagen.The following mechanisms are involved .

1. Reduction in the level or activities of matrix degrading enzymes in these lesions.

2. Induction of collagen production may occur by direct action of drugs on collagen synthesis

orby directly affecting the gene transcription rate

3.Indirectly through cytokines such as TGFβ

AGE CHANGES OF COLLAGEN

As age advances qualitative and quantitative changes of collagen are seen

 -Higher conversion of soluble to insoluble collagen

 -Increased mechanical strength.

 -Increased denaturing temperature

 Increased collagen fibrosis and decreased cellularity

 These changes are due to higher cross linking and stabilized forms of collagen
COLLAGEN AS BIOMATERIAL IN PERIODONTICS:

RECESSION COVERAGE PERIOCOL(COLLAGEN

MEMBRANE)

GELSPO LOCALISED DRUG

DELIVERY HEMOSTATIC GELATIN SPONGES

IN PERIODONTAL POCKETS

DISEASES ASSOSCIATED WITH COLLAGEN ALTERATIONS :

The following alterations can affect collagens and lead to connective tissue changes:

 Defect in the structure of collagen genes.

 Molecular defect in the processing enzymes .

 Mechanisms affecting the expression of collagen genes due to pathologies of

acquired disease.
INHERITED DISEASES DUE TO COLLAGEN ALTERATIONS

 OsteogenesisImperfecta.-COL1A1

 Ehlers Danlos Syndrome.-COL3A1

 Chondrodysplasia. - COL2A1

 Alport’s Syndrome. - COL4A5

 EpidermolysisBullosa- COL7A1

ACQUIRED DISEASES:

In these disorders, the gene expression is affected, not the gene structure.The

underlying cause of the disease is unknown; the diseases are caused by variety of factors and

all matrix components including collagens and proteoglycan are affected.(Narayanan &

Page 1983)Examples include chronic inflammatory diseases like rheumatoid arthritis,

sjogrens syndrome etc., and also fibrosed conditions like atherosclerosis, pulmonary fibrosis

METABOLIC DISORDER- DIABETES MELLITUS :

In the hyperglycemic state, numerous proteins and matrix molecules undergo a non-enzymatic

glycosylation, resulting in accumulated glycation end products (AGEs).

Collagen is cross-linked by AGE formation, making it less soluble and less likely to be

normally repaired or replaced. As a result, collagen in the tissues of patients with poorly

controlled diabetes is aged and more susceptible to breakdown

CONCLUSION

Collagen production becomes low in case of aging which no only affects periodontal health

but also it affects bone, skin, hair, nails joins. The major complication in collagen deficiency leads o

arthritis.

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.
 RFERENCE

1) Bartold 5th edition

2) Carranza’s Clinical Periodontology 11th edition

3) Clinical Periodontology And Implant Dentistry Jan Lindhe 5th edition

4) Maria Emanuel Ryan & Lorne M. Golub .Modulation of matrix metallo-

proteinase activities in periodontitis as a treatment strategy.

Periodontology 2000, vol 24, 2000,226-238.