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Collagen is most abundant protein in mammals, the main fibrous component of skin, bone, tendon and cartilage. Collagen comprises one- third of the total protein, accounts for three-quarters of the dry weight of skin, and is the most prevalent component of the extracellular matrix. The collagen family consists of 28 members and these are classified by Roman numbers on the basis of their chronology of discovery.
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1
COLLAGEN AND COLLAGEN
DISORDERS Dr. Achi joshi
Dept Of Periodontics
SAIMS
2
CONTENTS: Introduction
Structure
Biosynthesis of collagen
Types and functions of collagen
Degradation and remodelling of collagen
Biomedical applications
Collagen in periodontal tissue
Collagen disorders
Conclusion
3
INTRODUCTION
Collagen is most abundant protein in mammals and accounts for 25-30% of
their protein content.
Collagen is the main fibrous component of skin, bone, tendon and cartilage.
Collagen comprises one- third of the total protein, accounts for three-
quarters of the dry weight of skin, and is the most prevalent component of
the extracellular matrix.
4
The word collagen comes from the Greek word,
“kola,” meaning, “Glue producing”
French word, collagene designates glue-producing constraints because
collagenous tissue were used as source of glue and gelatin.
5
When it is heated in water, it gradually breaks down to produce soluble
derived protein i.e. gelatin or animal glue.
Miller and Matukas discovered collagen in 1969, since then 26 new
collagen types have been found.
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The collagen molecule is a rigid rod like structure that resists stretching.
Therefore this protein is an important structural component in tissues such as the
periodontal ligament, muscles and tendons in which the mechanical forces need to
be transmitted.
Collagen can also influence cell shape, differentiation and many other cellular
activities. Thus, forming an important group of multifunctional connective tissue
protein that participates in many biological functions.
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STRUCTURE OF COLLAGEN All collagens are composed of 3 polypeptide alpha chains
coiled around each other to form the tripe helix configuration.
The α chains are left handed helices that wrap around each
other into a right handed rope like triple helical rod.
Each such helix is around 1.4 nanometers in diameter and
300 nanometers in length
The triple helix may be of a continuous stretch or it may be
interrupted by non collagenous elements.
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There are around 3 amino acids per turn.
The triple-helical sequences are comprised of Gly-X-Y
repeats, X and Y being frequently proline and 4-
hydroxy-proline, respectively.
Glycine occupies every third position in the repeating
amino acid sequence, it is essential for the triple
helical conformation because larger amino acids will
not fit in the center of the triple helix.
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In the α chain of type I collagen there are 338 Gly – X – Y triplets repeated
in a sequence and additional 32 amino acids flank the long triplet sequence
at each end. They are known as telopeptides. There is both an amino
terminal ( -NH2 ) and a carboxy terminal (-COOH ) telopeptide.
Proline and hydroxyproline in the α chains are imino acids with a rigid
cyclical structure.
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Stabilization of the triple helix is by-
the presence of glycine as every third residue,
a high content of proline and hydroxyproline,
inter-chain hydrogen bonds, and
electrostatic interactions involving lysine and aspartate.
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COLLAGEN BIOSYNTHESIS Collagen biosynthesis, starting with transcription of genes within nucleus to
aggregation of collagen heterotrimers into large fibrils is a complex multistep process.
The entire process of collagen biosynthesis-
Gene expression
Translational and post translational events or intracellular steps in collagen synthesis
Extracellular collagen biosynthetic events
Regulation of synthesis
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STEPS
There are more than 40 genes described for collagen types I to XXVIII.
Collagen is a structural protein and its synthesis is similar to synthesis of
any other protein molecule and involves process of transcription and
translation of genes.
From collagen genes mRNA for each collagen type is transcribed, it
undergoes many processing steps to produce a final code for that specific
collagen type. This step is called mRNA processing.
The initial RNA transcript is processed to mRNA and it gives rise to the
primary polypeptide chains in the ribosomes.
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The polypeptide chain formed initially is a helical molecule with two non-
helical extensions one at the NH2 and the other at the –COOH terminal end
(telopeptide)
The –NH2 terminal extension has a leader or signal sequence that directs
the entry of the molecule into the rough endoplasmic reticulum.
14
The pre- pro-collagen molecule is converted to pro collagen molecule by
removal of signal peptide by signal peptidase and undergoes multiple steps
of post-translational modifications.
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HYDROXYLATION
Hydroxyproline and hydroxylysine are formed in the RER by the
hydroxylation of prolyl and lysyl residues. This is an essential step in
biosynthesis of collagen for it stabilises the molecules.
Requirements for hydroxylation are: Specific enzymes- prolyl hydroxylase and lysyl hydroxylase α-ketoglutarate Ferrous ions Molecular oxygen Ascorbic acid (Vitamin C)
16
GLYCOSYLATION OF HYDROXYLYSINE The enzyme galactosyl transferase catalyzes the addition of galactose to a
hydroxylysyl residue .
Glucosyl transferase catalyzes the further addition of glucose.
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Formation of procollagen
Following hydroxylation and glycosylation, three polypeptide chains form a
triple helix .
Secretion of procollagen
Procollagen passes into the Golgi complex before its secretion into the
interstitial spaces.
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In the interstitial spaces,
Procollagen collagen.
Procollagen amino-peptidase and procollagen carboxylase catalyze the
removal of the two peptide chains that form the extension of the
procollagen molecule.
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Cross-linkage of fibrils to form fibres
There is oxidative deamination of specific lysyl or hydroxylysyl residues to form
aldehydes; the reaction is catalyzed by lysyl oxidase.
20
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TYPES OF COLLAGEN The collagen family consists of 28 members and these are classified by
Roman numbers on the basis of their chronology of discovery.
Variations are brought by
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.
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FUNCTIONS Type Function
I Provides tensile strength to connective tissue
II Provides tensile strength to connective tissue
III Forms structural framework of spleen, liver, lymph nodes, smooth muscle,
adipose tissue. Provides tensile strength to connective tissue
IV Forms meshwork of the lamina densa of the basal lamina to provide
support and filtration
V Provides tensile strength, associated with type I collagen, also with
placental ground substance.
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VI Bridging between cells and matrix (has binding properties
for cells, proteoglycan, a type I collagen)
VII Forms anchoring fibrils that fasten lamina densa to
underlying lamina reticularis
VIII Tissue support, porous meshwork, provide compressive
strength
IX Associates with type II collagen fibers
25
X Calcium binding
XI Provides tensile strength, controlling lateral growth of type II fibrils
XII Associated with type I collagen fibers
XIII Cell matrix and cell adhesion
XIV Modulates fibril interactions
XV Proteolytic release of antiangiogenic factor
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XVI Unknown
XVII Cell to matrix attachment
XVIII Proteolytic release of antiangiogenic factor
XIX formation of hippocampal synapses
XXIV Regulation of type I fibrillogenesis, marker of osteoblast
differentiation and bone formation
XXVII cartilage calcification, Association with type II fibrils (?)
27
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.
28
The MMPs are considered to be essential for the degradation .
The collagenases are responsible for the first degradation step of collagen,
in which the fibers are cleaved into the characteristic 1/4 and 3/4
fragments.
Gelatinases and cysteine proteases further degrade the collagen
fragments.
29
Collagen degradation is an essential component of tissue development
during growth and of tissue maintenance in the adult.
Collagenases are widely distributed in the tissues and they bring about
collagen turnover, which is under physiological control, and can bring about
pathological destruction of connective tissue or provoke excessive new
collagen deposition and fibrosis.
30
PATHWAYS OF COLLAGEN DEGRADATION
Collagen degradation
The Collagenase Independent Intracellular Route
The Collagenase Mediated Extracellular Route
31
Imbalance between activated MMPs and their endogenous inhibitors leads
to pathologic breakdown of extracellular matrix during periodontitis.
32
BIOMEDICAL APPLICATIONS
Collagen is regarded as one of the most useful biomaterials.
The excellent biocompatibility and safety due to its biological
characteristics, such as
biodegradability
biocompatibility
weak antigenicity.
33
USES To repair tissues such as bone, tendon, ligament, skin, vascular and connective tissues.
Drug delivery applications: to develop scaffolds for delivery of genes, cell, growth
factors, anesthetics, analgesics, antibiotics etc.
For LDD in periodontal pockets
Tissue augmentation: For use in plastic surgery
To enhance blood coagulation and platelet activation
To enhance durability of allograft tissues.
In guided tissue regeneration.
34
Can be used for the generation of bone substitutes, wound dressings,
nerve regeneration.
Artificial skin.
For use as a research tool to study diseases such as diabetes, aging and to
evaluate drugs.
35
ADVANTAGES Available in abundance and easily purified from living organisms
(constitutes more than 30% of vertebrate tissues)
Non-antigenic.
Biodegradable and bio-reabsorbable.
Non-toxic and biocompatible.
Biological plastic due to high tensile strength and minimal expressibility.
Hemostatic — promotes blood coagulation.
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Formulated in a number of different forms.
Biodegradability can be regulated by cross-linking.
Easily modifiable to produce materials as desired by utilizing its functional
groups.
Compatible with synthetic polymers.
37
DISADVANTAGES
High cost of pure type I collagen.
Variability of isolated collagen (e.g. crosslink density, fiber size, trace impurities,
etc.)
Hydrophilicity which leads to swelling and more rapid release.
Variability in enzymatic degradation rate as compared with hydrolytic degradation.
Complex handling properties.
Side effects, such as bovine spongeform encephalopathy (BSF) and mineralization.
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COLLAGEN IN PERIODONTAL TISSUES The collagen of periodontium 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.
39
40
BONE COLLAGEN
Out of 22 to 25% of organic component 94 to 98% is mainly collagen type I.
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.
41
CEMENTAL COLLAGEN Predominant collagen present in cementum is type I
collagen (forms 90% of the organic matrix).
Other collagens associated with cementum include type III,
a less cross-linked collagen found in high concentrations
during development, repair, and regeneration of
mineralized tissues and type XII that binds to type I
collagen and to non-collagenous matrix proteins.
Collagens found in trace amount in cementum are types V,
VI and XIV.
42
GINGIVAL COLLAGEN
Collagens are the most abundant biochemical constituents of gingival
connective tissue.
The collagen matrix of gingival CT is well organized into fiber bundles,
which constitute the gingival supra alveolar fiber apparatus.
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Based on their preferential orientation, architectural arrangement and sites
of insertion they are classified as-
1.Dentogingival
2.Dentoperiosteal
3.Alveologingival
4.Periosteogingiva
5.Circular and semicircular
6.Transgingival
7.Transseptal
8.Interpapillary
9.Intercircular
10.Intergingival
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PERIODONTAL FIBERS Periodontal ligament is composed of collagen fibers
bundles connecting cementum and alveolar bone
proper.
The vast majority of collagen fibrils in the periodontal
ligament are arranged in definite and distinct fiber
bundles and these are termed as principal fibers.
It contains type I and type III collagen, relative
proportion of type III to type I varies from 10-25%
APICAL
OBLIQUE INTER RADICULAR
HORIZONTAL
TRANSEPATAL
ALVEOLAR CREST
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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 di-hydroxy-lysine while hydroxyl-lysine is a minor component
The presence of covalent cross-links between collagen molecules stabilizes the
ligament fibres and increases the tensile strength
46
Majority of PDL collagen fibers are arranged in to
Horizontal & Oblique directed groups to adapt to
axial forces.
The complex 3D arrangement of fibers means that
some bundles would always be placed in Tension,
irrespective of the direction of an applied force. This
enables local areas of the PDL to resist compressive
forces
47
FUNCTIONAL ADAPTATIONS OF COLLAGEN
Tooth support system is a multiphasic system comprising of
fibres , ground substances, blood vessels, fluids acting
together to resist mechanical forces.
Internal Orientation of collagen fibers influences the
mechanical properties of the tissue . Collagen fibers best
resist axially directed force as majority of PDL collagen fibers
are arranged in to Horizontal & Oblique direction.
48
OVERLAPPING ARRANGEMENT of fibers as visible in Electron Microscope
looks like the spokes of a cycle wheel.
This is very crucial in withstanding Rotational & Intrusive Forces.
This overlapping arrangement helps in spreading the load uniformly and
reduce the strain on PDL.
49
SHARPEY’S FIBER
The terminal ends of the collagenous principal
fibers are inserted in to bones to form Sharpey’s
Fibers.
These 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 they are inserted in to the bone by
preventing their mineralization.
50
COLLAGEN CRIMPING Collagenous tissues exhibit a quantifiable periodicity of structure of variable scale,
the waveform that describes this periodicity has been referred to as crimp.
In the polarizing microscope crimping can be seen by regular banding of dark lines
across the bundles.
Causes-
Sharp Zig-Zag arrangement of collagen fibers with quantifiable periodicity angular
deflection from axis
Microanatomical organization of collagenous sheets and bundles in sinusoidal wave
forms.
51
Significance-
It is an early ,easily extensible , non linear region that causes the straightening
out of the crimp, this enables the ligament to absorb impact tensile loads
without extending collagen fibrils and without producing heat.
Fibroblast processes in the developing collagenous tissues play a role in
fabricating the crimped arrangement and consequently that crimping may be an
important feature in tooth eruption.
It also has been proposed that crimp some times can generate contractile forces
in collagen molecules.
52
COLLAGEN DESTRUCTION IN INFLAMMATION
Gingivitis
Collagenolytic activity is increased in inflamed gingival tissue by the enzyme collagenase. Following
changes are seen in three different stages of 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.
This is necessary so that tissues can be pushed apart to accommodate the infiltrating cells and it is
considered to be a space creating process.
The main fiber groups affected appear to be circular and dentogingival fiber assemblies.
53
In established lesion – collagen fibers are destroyed around the
infiltrate of intact and disrupted plasma cells, neutrophils, lymphocytes,
monocytes and mast cells.
Collagen loss continues in both lateral and apical directions as the
inflammatory cell infiltrate expands resulting in collagen depleted spaces
extending deeper into the tissues which are then available for leukocyte
infiltration.
54
In periodontal pockets
Apical to the junctional epithelium, collagen fibers are destroyed and the area
becomes occupied by inflammatory cells and edema.
As the consequence of the lossof collagen,the apical cells of the junctional
epithelium proliferate along the root, extending finger like projections two or three
cells in thickness.
55
COLLAGEN AS BIOMATERIAL IN PERIODONTICS
1. Drug delivery- For LDD in periodontal pockets
The key benefit of localised drug delivery over systemic therapy is that
high concentrations of drug can be maintained at the target site, while
avoiding risk of systemic toxicity and associated side-effects.
The drugs can be loaded into collagen membranes by hydrogen bonding,
covalent bonding or simple entrapment.
56
PPAB is collagen fibril based formulation containing tetracycline hydrochloride (2 mg of tetracycline) in 25 mg of collagen fibrils.
Periocol®- TCSterile collagen Fibres with Tetracycline Hydrochloride for periodontal infections.
57
2. Tissue augmentation- recession coverage
Collagen membranes are used as an alternative to connective tissue grafts
in mucogingival surgeries.
It shows similar histologic and clinical outcomes, achieving complete root
coverage when compared with connective tissue grafts.
It gets completely incorporated in the adjacent host connective tissues
without any signs of inflammation.
58
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3. 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.
Demineralized bone collagen is used as a bone graft material for the
treatment of acquired and congenital bone defects either by itself or in
combination with hydroxyapatite crystals.
60
Osseograft/DMBM is one such de-mineralized bone derived Type-I collagen for bone void filling applications.
Dembone is Demineralized Freeze-dried Cortical Bone Powder, prepared from cortical bone harvested from carefully screened human donors, demineralized in HCl acid, freeze dried and triple sterilized before vacuum packing.
61
SyboGraf™Sterile Synthetic Nanocrystalline Hydroxyapatite Bone Graft.particle size ranging from 200-300 and 600-700 microns.
62
4. In guided tissue regeneration- GTR membranes
Guided tissue regeneration (GTR) is a procedure that attempts to reconstitute the lost
tissues and is based on the concept of selective repopulation.
The first report of a human tooth treated by guided tissue regeneration was by Nyman
et al in 1982, with the term GTR coined by Gottlow et al in 1986.
To exclude the fast-growing cells of the gingival epithelium from migrating to the
wound, GTR procedures use barrier devices that are placed between the periodontal
flap and the osseous defect to maintain a space for repopulation of the defect with
cells having regenerative potential.
63
Healiguide thin sheet made of high purity Type-I collagen
derived from selected animal tissues. Periocol® / Helisorb®-GTRType 1 collagen membrane of fish origin for GTR applications
Cologuide
5. Hemostat
During the healthy process of blood clotting, platelets become activated by
thrombin and aggregate at the site of injury.
Stimulated by the protein fibrinogen, the platelets then clump by binding to the
collagen that becomes exposed following rupture of the endothelial lining of blood
vessels.
Collagen is therefore a natural haemostat and a wide variety of collagen-based
products are used in surgery and dentistry to control excessive bleeding or
haemorrhage. 64
65
Absorbable sterile fibrillar collagen wound filler, constituted using high purity type-1 reconstituted collagen
•Hemostatic agent•Control bleeding and stabilizes blood clots•Protects wound bed
GelSpon®
Sterile Absorbable Haemostatic Gelatin Sponges
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COLLAGEN DISORDERS
Collagen diseases may be genetic, auto-immune or miscellaneous like
defects due to nutritional deficiencies, drug induced defects etc. An inborn
error of metabolism involving abnormal structure or metabolism of collagen
results in collagen disorders. All these affect the biosynthesis, assembly,
post-translational modification, secretion, or other processes involved in
normal collagen production.
67
GENETIC OR HERITABLE COLLAGEN DISORDERS
Heritable collagen disorders are caused by mutations in the genes coding
for collagen α chain.
The mutations affect the extracellular matrix by decreasing the amount of
secreted collagen, impairing molecular and supra-molecular assembly
through the secretion of a mutant collagen, or by inducing endoplasmic
reticulum stress and the unfolded protein response.
68
OSTEOGENESIS IMPERFECTA The disease is characterized by-
extremely fragile bones
reduced bone mass
blue sclera,
hearing loss and
scoliosis.
69
This is due to mutations in one of the two genes, COL1A1 and COL1A2,
which encode the two chains of type I collagen, the major protein of bone.
The most common mutations of this disease is due to substitution of
glycine with a bigger amino acid.
70
EHLERS-DANLOS SYNDROME
Heterogeneous group of heritable disorders of connective tissue characterized by –
articular hypermobility
skin hyperextensibility, and
tissue fragility affecting skin, ligaments, joints, blood vessels, and internal organs.
Cause- mutations in the COL5A1 and COL5A2 genes encoding the α1 and α2
chains of type V are defined.
71
ORAL MANIFESTATIONS
Gorlin sign
Early onset generalized periodontitis resulting in the premature loss of
deciduous and permanent teeth.
The gingiva is fragile and hemorrhage may be difficult to control during surgical
procedures.
Absence of the inferior labial and lingual frenula has been reported in EDS II,
EDS III and suggested to be a highly specific and sensitive marker for these
disorders.
72
ALPORT SYNDROME
Alport syndrome is a progressive hereditary nephritis with Extra-
renal complications, like sensory-neural hearing loss and ocular
abnormalities.
Caused by deletion mutations in COL4A5 and COL4A6 genes or
COL4A3 and COL4A4 genes encoding the α3 (IV) and α4 (IV) chains.
X-linked
This syndrome affects some of the basal membranes and is
characterized by renal failure, loss of hearing and lens
abnormalities.
73
EPIDERMOLYSIS BULLOSA Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of
inherited disorders that are characterized by blistering of the skin and certain other
tissues.
Caused by
mutations in COL7A1, affecting the structure of type VII collagen.
Type VII collagen forms delicate fibrils that anchor the basal lamina to collagen
fibrils in the dermis.
These anchoring fibrils are reduced in this form of the disease, causing friction
and blistering.
74
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CHONDRODYSPLASIAS
A rare, inherited disorders of skeletal development and linear growth.
Involve disturbances of the cartilage components of the growing skeleton,
it is Mutations of the gene for type II collagen, COL2A1, produce a broad
spectrum of clinical phenotypes that fall under the general designation,
spondyloepiphyseal dysplasia (SED).
76
KNOBLOCH SYNDROME
Knobloch syndrome is an autosomal recessive disorder
characterized by high myopia, vitreo-retinal
degeneration, occipital bone damage, and congenital
encephalocele.
pathological mutations in the COL18A1 gene at 21q22.3
have been identified.
These mutations cause the loss of one or all collagen
COL18A1 isoforms or endostatin.
77
BETHLEM MYOPATHY
Bethlem myopathy is an autosomal
dominant inherited relatively mild disease
that is characterized by muscle weakness
and distal joint contractures.
Type VII collagen plays a role in
connecting cells and extracellular matrix
and that mutations in genes encoding
collagen VII result in Bethlem myopathy.
78
STICKLER SYNDROME
It is a unique autosomal dominant
syndrome of premature osteoarthritis,
retinal degeneration, hearing loss and
orofacial abnormalities
caused by mutations in the COL2A1,
COL11A1 and COL11A2 procollagen
genes of type 2 and 1 collagen.
79
SCHMID METAPHYSEAL CHONDRODYSPLASIA
This autosomal dominant disorder
usually presents after the age of
2–3 years with mild short stature,
bowing of the lower extremities,
and a waddling gait.
80
OSTEOLATHYRISMOsteolathyrism is a collagen cross-linking deficiency caused by
dietary over-reliance on the seeds of Lathyrus sativus (kesari dal)
in some parts of India.
Osteolathyrogenic compounds like Beta-aminopropionitrile (BAPN)
and Beta-oxalyl aminoalanine [BOAA] found in Kesari dhal inhibit
enzyme lysyl oxidase required for the formation of cross links in
the triple helices
EFFECT
weakness and fragility of skin, bones, and blood vessels
Paralysis of the lower extremities associated with neurolathyrism
81
AUTO IMMUNE DISORDERS
Collagen diseases share similarities with autoimmune diseases, because
autoantibodies specific to each collagen disease are produced.
Multiple organs may be affected.
82
SYSTEMIC LUPUS ERYTHEMATOSUS
Lupus erythematosus is a multifactorial
autoimmune collagen vascular or
connective tissue disease, which may affect
the oral mucosa in either its cutaneous and
systemic forms with varied prevalence
Oral lesions include ulceration, pain,
erythema and hyperkeratosis. Other oral
complaints are xerostomia, stomatodynia,
candidiasis, periodontal disease and
dysgeusia.
83
ORAL SUB MUCOUS FIBROSIS
This disease is considered to be a consequence of
disturbances in the homeostatic equilibrium between
synthesis and degradation of extracellular matrix,
wherein collagen forms a major component, thus can
be recognized as a collagen-metabolic disorder.
It is characterized by a juxta epithelial inflammatory
reaction followed by fibroelastic change in the lamina
propria and associated epithelial atrophy.
84
MISCELLANEOUS
85
SCURVY
Key function of ascorbic acid is its involvement in the synthesis of collagen fibers
from proline via hydroxyproline.
Other metabolic reactions for which vitamin C is required are the hydroxylation of
lysine into hydroxylysine in collagen.
In individuals who suffer from a deficiency of this vitamin, the α-chains of the
tropocollagen molecules are unable to form stable helices and the tropocollagen
molecules are incapable of aggregating into fibrils.
86
Avitaminosis C is associated with the failure
of wound healing or the rupture of
capillaries due to intrinsic intercellular
weakness with lack of connective tissue
support of the capillary walls.
Oral manifestations –
Fetid odor and loosened teeth,
gingivae are boggy, ulcerated and bleed
easily
interdental and marginal gingiva become
bright red, smooth, swollen and shiny.
87
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 i.e., less resistant to
destruction by periodontal infections.
88
GINGIVAL ENLARGEMENTS
1. Hereditary gingival fibromatosis
both dominant autosomal inheritance and recessive autosomal inheritance
It is a gradually progressive benign enlargement that affects the marginal,
attached, and interdental gingiva.
Histopathologically, it implies an increase in both extracellular matrix and
cell numbers.
89
2. drug induced enlargement
A. phenytoin
Fibroblasts become sensitive to phenytoin, and this results in subsequent
increased production of collagen.
The enzyme collagenase secreted by phenytoin-sensitive fibroblasts is
relatively inactive to degrade collagen.
An imbalance in production and degradation results in the over
accumulation of collagen and hence in an increase in the bulk of
connective tissue.
90
B. Calcium channel blockers
After an interaction between nifedipine and gingival fibroblasts,
overproduction of collagen and extracellular ground substance occurs and
leads to an increase in the size of the gingiva.
C. Cyclosporin induced
It was found that CsA could react with a phenotypically distinct
subpopulation of gingival fibroblasts to enhance protein synthesis.
91
CONCLUSION
Collagens have ubiquitous distribution throughout the animal kingdom. Collagens
serve important mechanical functions within the body, particularly in connective
tissues and also exert important functions in the cellular microenvironment.
It is an important constituent of periodontium therefore knowledge of the structure,
biosynthesis and interactions of collagen with other components, its regulation and
degradation mechanisms and changes it undergoes with age and diseased state is
essential, for the understanding of the functioning of the periodontium.