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King Saud University
Riyadh
Saudi Arabia
Dr. Gihan Gawish
Assistant Professor
Gihan Gawish.Dr
Gihan Gawish.Dr
Connective tissue
 Derived from mesoderm
 Connective tissue functions not only as a mechanical
support for other tissues
 But also as an avenue for communication and transport
among other tissues.
 Blood vessels and nerves travel through connective
tissue.
Gihan Gawish.Dr
Components of Connective Tissue
 Connective tissue consists of
embedded in an extracellular matrix.
cells
 The matrix, in turn, consists of fibers and
ground substance.
Gihan Gawish.Dr
Connective tissue cell types
– Fibroblasts (which secrete the fibers and
ground substance of the extracellular matrix).
– Adipocytes (which store fat).
– Mast cells (which trigger inflammation).
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– Macrophages (which ingest and remove
foreign material or damaged cells).
– lymphocytes, monocytes, and neutrophils,
which are all involved in immune defense and
inflammation.
Gihan Gawish.Dr
Types of the extracellular fibers of
connective tissue
 Collagen fibers confer main tensile strength, and
are the stuff of scars. Collagen is produced by
fibroblast.
 Elastic fibers confer elasticity.
 Reticular fibers (really, a special form of
collagen III) provide a delicate supporting
framework for loose cells.
Gihan Gawish.Dr
Ground substance
 It is the background material within which all other
connective tissue elements are embedded.
 In ordinary connective tissue, It consists mainly of
water whose major role is to provide a route for
communication and transport (by diffusion) between
tissues.
 This water is stabilized by a complex of
glycosaminoglycans (GAGs), proteoglycans, and
glycoproteins, all of which comprise only a small
fraction of the weight of the ground substance.
Gihan Gawish.Dr
Ground substance may be highly modified
in the special forms of connective tissue
 In blood, the ground substance is fluid
(plasma).
 In bone, the ground substance includes minerals
by deposition of calcium salts.
 In cartilage, the ground substance is much more
solid than in ordinary connective tissue but still
retains more resiliency than bone .
Gihan Gawish.Dr
Classification of connective tissue
depending on the proportion of various cellular and
extracellular components
 Dense connective tissue (Regular, Irregular and
Elastic).
 Loose connective tissue (Areolar, Adipose and
Reticular).
 Cartilage (Hyaline, Fibrocartilage and Elastic).
 Other (Bone, Blood and Lymphatics)
Gihan Gawish.Dr
Dense connective tissue
 Also called dense fibrous tissue, has collagen
(collagen type I) fibers as its main matrix
element.
 Dense regular connective tissue has collagen
fibers that are bundled in a parallel fashion.
It forms strong, rope-like structures such as
tendons and ligaments.
 Tendons attach skeletal muscles to bones;
ligaments connect bones to bones at joints.
Ligaments are more stretchy and contain
more elastic fibers than tendons.
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 Dense irregular connective tissue has fibers that are
not arranged in parallel bundles as in dense regular
connective tissue. also make up the large portion of
the skin (dermis)
 Elastic connective tissue is primarily composed of
elastin fibres, giving them great elasticity. It appears
in the walls of the aorta.
Gihan Gawish.Dr
loose connective tissue
 It is a pliable, mesh-like tissue with a fluid matrix
and functions to cushion and protect body organs.
 It has fibroblasts that are widely dispersed; they
are irregular branching cells that secrete strong
fibrous protein and proteoglycans as an
extracellular matrix.
 The cells of this type of tissue are generally
separated by quite some distance by a gel-like
gelatinous substance primarily made up of
collagenous and elastic fibers.
Gihan Gawish.Dr
 Areolar connective tissue serves as a reservoir of
water and salts for surrounding tissues. Almost all cells
obtain their nutrients from and release their wastes into
areolar connective tissue.
 It is found beneath the dermis layer and is also
underneath the epithelial tissue of all the body systems
that have external openings.
 It is also a component of mucus membranes found in
the digestive, respiratory, reproductive, and urinary
systems.
 It also surrounds the blood vessels and nerves
Gihan Gawish.Dr
 Adipose tissue contains adipocytes, used for
cushioning, thermal insulation, lubrication
(primarily in the pericardium) and energy
storage
 Reticular connective tissue is a network of
reticular fibres (fine collagen, type III) that form
a soft skeleton to support the lymphoid organs
(lymph nodes, bone marrow, and spleen)
Gihan Gawish.Dr
Gihan Gawish.Dr
Its mechanical properties are intermediate
between bone and dense connective tissue
like tendon.
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Cartilage composition
specialized cells
chondrocytes
collagen fibers
Ground substances
Proteoglycan+
elastin fibers
Cartilage is classified into three types
elastic cartilage hyaline cartilage
fibrocartilage
Cartilage abundant
articular surface of the bones,
the rib cage,
the ear.
Gihan Gawish.Dr
nose,
bronchial tubes
intervertebral discs
 Blood is traditionally classified as a specialized form
of connective tissue, with no fibers, highly fluid
ground substance, and mobile cells.
 Bone are special forms of connective tissue, made by
specialized osteoblasts with uniquely solidified
ground substance.
 Lymphoid tissue is a connective tissue with large
numbers of lymphocytes that have accumulated in
the tissue (lymph nodes, bone marrow, and
spleen.) .
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Gihan Gawish.Dr
Classification of connective tissue
 Connective tissue proper.
 Specialized connective tissues.
 Embryonic connective tissues.
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Gihan Gawish.Dr
Collagen
 Collagen is the main protein of connective
tissues in animals and the most abundant protein
in mammals
 It making up about 25% of the whole-body protein
content.
 Collagen is an inextensibile fibrous protein that is
found in connective tissue. Fibrous proteins are
generally water-insoluble and are found as an aggregate
due to hydrophobic R group that stick out of the
molecule
Gihan Gawish.Dr
 Tough bundles of collagen called collagen fibers
are a major component of the extracellular
matrix that supports most tissues and gives cells
structure from the outside, but collagen is also
found inside certain cells.
 Collagen has great tensile strength, and is the
main component of cartilage, ligaments,
tendons, bone and teeth.
Gihan Gawish.Dr
 It strengthens blood vessels and plays a role in
tissue development.
 It is present in the cornea and lens of the eye in
crystalline form. It is also used in cosmetic
surgery and burns surgery.
 If collagen is partially hydrolyzed by boiling, the
three tropocollagen strands separate into
globular, random coils, producing gelatin, which
is used in many foods, including flavoured
gelatin desserts.
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Tropocollagen
The triple-helix tropocollagen molecule is
the basic unit of the collagen fiber.
It Composed of about 1000 amino acids
each, the individual chains of tropocollagen
contain a left-handed helical structure, but
are wound together with the other two
chains of the fiber in a right-handed
manner.
Gihan Gawish.Dr
 Each five tropocollagens combine to form a fiber
segment.
 It is important to realize that in an actual fiber
segment the ends of the tropocollagen would be
staggered.
 The staggered ends would permit overlap in the
association of the tropocollagens in adjacent
segments, and thus aid in forming a strong fiber.
Gihan Gawish.Dr
 The tropocollagen or "collagen molecule"
subunit is a rod about 300 nm long and 1.5 nm in
diameter
 A triple helix or "super helix", a cooperative
structure stabilized by numerous hydrogen
bonds.
 Collagen's
properties
of
rigidity
and
inextensibility are due to this highly ordered
structure.
Gihan Gawish.Dr

There is some covalent cross linking within the
triple helices, and a variable amount of
covalent cross linking between tropocollagen
helices, to form the different types of collagen
found in different mature tissues

Collagen's insolubility was a barrier to study
until it was found that tropocollagen from
young animals can be extracted because it is
not yet fully cross linked.
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Synthesis of collagen
 The repeating amino acid sequence is
Gly-X-Y, where X is often proline and Y
is proline or hydroxyproline (a modified
form of proline( or may be any of various
other amino acid residues
 Every third residue lies near the center of
the triple helix and can only be glycine,
because all other amino acid side chains
would be too bulky.
 Hydroxyproline helps to stabilize the
triple helix via hydrogen bond.
Gihan Gawish.Dr
Glycine
Proline
Hydroxyproline
Melting temperature
of collagen
 This is supported by the fact
that helical polymers with the
repeating sequence (Pro-HypGly) are much more stable to
thermal denaturation than those
with the sequence (Pro-ProGly).
 Indeed the melting temperature
of collagen from various
sources is directly dependent on
the hydroxyproline content.
Gihan Gawish.Dr
 In collagen, Gly is required at every third
position because the assembly of the triple
helix puts this residue at the interior (axis) of
the helix, where there is no space for a
larger side group than glycine’s single
hydrogen atom.
 For the same reason, the rings of the Pro
and Hyp must point outward. These two
amino acids thermally stabilize the triple
helix
Gihan Gawish.Dr
 Collagen is unusual not only in having modified amino
acid residues, such as hydroxyproline and
hydroxylysine, but also in having so many of them.
 Hydroxylation of proline requires ascorbic acid
(vitamin C). Deficiency of vitamin C reduces
hydroxyproline production, leading to weakened
collagen fibers and the condition known as scurvy.
 Part of collagen's toughness arises from cross-links
between lysine residues of adjacent chains. This cross
linking reaction occurs throughout life and makes
bones, skin, and tendons less elastic.
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Types of collagen
 There are 28 types of collagen. These varieties
are produced by different genes, have somewhat
different properties, and occur in different
locations.
 Type I collagen forms the familiar eosinophilic
collagen fibers of ordinary fibrous connective tissue
(e.g., dermis, tendon, organ sheath, fascia) .
 Type II collagen reinforces cartilage.
 Type III collagen forms reticular fibers and also occurs
in bone.
 Gihan
Type
IV& V forms the basement membrane.
Gawish.Dr
Staining
 The dye methyl violet may be used to stain the
collagen in tissue samples.
 The best stain for use in differentiating collagen
from other fibers is Masson's trichrome stain.
Gihan Gawish.Dr
Scurvy
 Collagen diseases commonly arise from
genetic defects that affect the biosynthesis.
 Vitamin C deficiency causes scurvy, a serious
and painful disease in which defective
collagen prevents the formation of strong
connective tissue.
Gihan Gawish.Dr
 The symptoms include,
 dark purplish spots on skin; especially the legs,
 spongy gums; often leading to tooth loss,
 bleeding from all mucous membrane, pallor,
bleeding gums,
 sunken eyes,
 opening of healed scars;
 separation of knitted bone fractures,
 nosebleeds,
 non-stopping diarrhea,
 and nail loss.
Gihan Gawish.Dr
 In the human body, a malfunction of the
immune system, called an autoimmune
disease, results in an immune response in
which
healthy
collagen
fibers
are
systematically destroyed with inflammation of
surrounding tissues.
 The resulting disease processes are called
Lupus erythematosus, and rheumatoid
arthritis, or collagen tissue disorders.
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Pathophysiology
 Normal collagen synthesis depends upon the
hydroxylation of proline and lysine residues
in the endoplasmic reticulum, to form
hydroxyproline
and
hydroxylysine,
respectively.
Gihan Gawish.Dr
 Prolyl and lysyl hydroxylase, the enzymes that
catalyze the hydroxylation, require ascorbic
acid (vitamin C) to function correctly. With no
ascorbic acid, the enzymes cannot hydroxylate
proline and lysine, and so normal collagen
synthesis cannot be performed.
 Many bacteria and viruses have virulence
factors which destroy collagen or interfere
with its production.
Gihan Gawish.Dr
Ehlers-Danlos syndrome
 It is a group of rare genetic disorders affecting humans
and domestic animals caused by a defect in collagen
synthesis.
 Depending on the individual mutation, the severity of
the disease can vary from mild to life-threatening.
 There is no known cure.
 Treatment is supportive.
Gihan Gawish.Dr
Symptoms
 Symptoms vary widely based on which type of Ehlers
Danlos Syndrome (EDS) the patient has.
 In each case, however, the symptoms are ultimately due
to faulty or reduced amounts of collagen.
 For example, in the most common type of EDS,
Hypermobility Type, symptoms often include unstable,
flexible joints with a painful tendency to dislocate and
subluxate.
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 This is due to ligaments which are lacking proper
collagen--the molecule that provides strength to
ligaments--are overly stretchable.
 The so-called Classic EDS Type features skin that
forms cigarette-paper-like scars.
 Another type of collagen is usually responsible for
lending strength to skin (and scars).
 The most serious type of EDS, Vascular EDS, can
result in premature death via vascular (blood vessel)
and organ rupture.
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Individual with EDS displaying
hypermobile joints
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 Again, another type collagen is necessary to give
strength to the walls of blood vessels and the
walls of hollow organs (such as the large bowel,
aka colon).
 (It should be noted that Vascular EDS is also one
of the most rare types of the disease.)
 For instance, many of the types feature velvety
or hyperextensible skin.
Gihan Gawish.Dr
Collagenase
Gihan Gawish.Dr
 Mammalian collagenases belong to a family of
extracellular metalloproteinases.
 They are the only enzymes that can specifically cleave
native collagen.
 They catalyze a single proteolytic cleavage in the
helical collagen chains, resulting in two fragments that
are subsequently accessible to less specific proteases.
 The action of collagenase is regarded as a 'committed
step' since, without it, degradation of collagen cannot
take place
Gihan Gawish.Dr
Gihan Gawish.Dr
 Mammalian collagenases occur in a variety of tissues
and cells.
 Human skin collagenases are synthesized and secreted
as proenzymes.
 Only after activation, the enzymes can act on their
substrate, collagen.
 The active enzymes in turn can be readily inactivated by
a variety of inhibitors
 The strong regulation of synthesis, secretion and
activation-inactivation reflects the importance of
collagenases in the metabolism of tissue matrix
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proteins.
Cells Producing Collagenases:
 It has been reported that the enzymes are
produced in a variety of cells, namely neutrophil
granulocytes,
macrophages,
fibroblasts,
keratinocytes and others.
 These cells play an essential role in the different
stages of wound healing
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Gihan Gawish.Dr
Bacterial collagenases
 Collagenases are enzymes that break the peptide
bonds in collagen.
 They assist in destroying extracellular structures
in pathogenesis of bacteria such as Clostridium.
 They are an exotoxin (a virulence factor) and
help to facilitate the spread of gas gangrene.
Gihan Gawish.Dr
Gas gangrene
 Gas gangrene is a bacterial infection that
produces gas within tissues in gangrene.
 It is a deadly form of gangrene usually caused by
Clostridium bacteria (genus of Gram-positive
bacteria).
 It is a medical emergency.
Gihan Gawish.Dr
 These environmental bacteria may enter the
muscle through a wound and go on to proliferate
in necrotic tissue and secrete powerful toxins.
 These toxins destroy nearby tissue, generating
gas at the same time.
 A gas composition of 5.9% hydrogen, 3.4%
carbon dioxide, 74.5% nitrogen and 16.1%
oxygen was reported in one clinical case
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Collagenase-2
 Collagenase-2 is a member of a protein family
called matrix metalloproteinases, a large group
of enzymes that break down collagen and other
components of the body's connective tissue.
Gihan Gawish.Dr
 collagenase-2 plays a
role in the development
of multiple sclerosis, an
autoimmune
disease
that causes various
physical and mental
symptoms, and often
progresses to physical
and cognitive disability.
Gihan Gawish.Dr
Gihan Gawish.Dr
 Elastin is another fibrous protein.
 As the name suggests, elastin is elastic.
 In ordinary connective tissue, elastic fibers help restore
normal shape after distortion.
 In high enough concentrations, elastin confers a
yellowish color (as in the elastic ligament)
 Like rubber bands, elastic fibers can deteriorate with age
and exposure to sun.
Gihan Gawish.Dr
Locations in body
 Elastin serves an important function in arteries
and is particularly abundant in large elastic
blood vessels such as the aorta.
 Elastin is also very important in the lungs,
elastic ligaments, the skin, the bladder, elastic
cartilage, and the intervertebral disc above the
sacroiliac.
Gihan Gawish.Dr
Composition
 Elastin is primarily composed of the amino
acids glycine (about 30%), valine (13%),
alanine(23%)
&
proline
and
hydroxyproline(10%).
 It is a specialized protein with a molecular
weight of 64 to 66 kDa, and an irregular or
random coil conformation made up of 850
amino acids.
Gihan Gawish.Dr
Gihan Gawish.Dr
 The fundamental polypeptide chain in elastin
is tropoelastin (MW=70000)
 Elastin is made by linking many soluble
tropoelastin protein molecules, in a reaction
catalyzed by lysyl oxidase, to make a
massive insoluble, durable cross-linked
array.
 The amino acid responsible for these crosslinks is lysine.
Gihan Gawish.Dr
Cross-links in Elastin
 Desmosine and isodesmosine are both
found in elastin.
 A desmosine cross-link is formed from three
allysyl side chains plus one unaltered lysyl side
 Isodesmosine is a lysine derivative found in
elastin
 Lysine
Gihan Gawish.Dr
Lysyl oxidase
Allysine
About 25 – 30 desmosine cross links are found / tropoelastin
chain, to provide about one cross-link for every 28-34
residues
Allysine
Allysine
Desmosine
Allysine
Gihan Gawish.Dr
Lysine
Elastin Hydrolyzed
 1- Elastin can be hydrolyzed slowly by
pepsine at pH 2 .
 2- The pancreas secretes a zymogene
called proelastase trypsin elastase
 Elastase capable of hydrolyzed alanine
and valine
Gihan Gawish.Dr
Gihan Gawish.Dr
1. Hyaluronan
 It is one of the chief components of the
extracellular matrix,
 contributes significantly to cell proliferation
and migration,
 and may also be involved in the progression
of some malignant tumors.
Gihan Gawish.Dr
 Hyaluronan (also called hyaluronic acid or
hyaluronate)
is
a
non-sulfated
glycosaminoglycan
distributed
widely
throughout connective, epithelial, and neural
tissues.
 glycosaminoglycans are long unbranched
polysaccharides consisting of a repeating
disaccharide unit.
Gihan Gawish.Dr
The repeating disaccharide unit of
hyaluronan
Gihan Gawish.Dr
 The average 70 kg (154 lbs) man has
roughly 15 grams of hyaluronan in his body,
one-third of which is turned over (degraded
and synthesized) every day.
 Hyaluronic acid is also a component of the
group A streptococcal extracellular capsule
and is believed to play a role in virulence
Gihan Gawish.Dr
Functions of Hyaluronic acid
 Hyaluronan is an important component of
articular cartilage, where it is present as a
coat around each cell (chondrocyte).
 Hyaluronan is also a major component of
skin, where it is involved in tissue repair.
Gihan Gawish.Dr
 hyaluronan
also
contributes
to
tissue
hydrodynamics, movement and proliferation of
cells, and participates in a number of cell surface
receptor;CD44.
 Upregulation of CD44 itself is widely accepted as a
marker of cell activation in lymphocytes.
 High concentrations of hyaluronan in the brains of
young rats, and reduced concentrations in the
brains of adult rats suggest that hyaluronan plays
an important role in brain development.
Gihan Gawish.Dr
2.Chondroitin sulfate
 Chondroitin sulfate is a sulfated
glycosaminoglycan (GAG) composed of a
chain
of
alternating
sugars
(Nacetylgalactosamine and glucuronic acid).
Chondroitin-4sulfate: R1 = H; R2 =
SO3H; R3 = H.
Chondroitin-6sulfate: R1 = SO3H;
R2, R3 = H.
Gihan Gawish.Dr
It is usually found attached to proteins as part of a
Proteoglycan.
A chondroitin chain can have over 100 individual sugars,
each of which can be sulfated in variable positions and
quantities.
 Chondroitin sulfate is an important structural
component of cartilage and provides much of its
resistance to compression.
 Along with glucosamine, chondroitin sulfate has
become a widely used dietary supplement for
treatment of osteoarthritis
Gihan Gawish.Dr
3. Heparin
 Heparin, a highly-sulfated
glycosaminoglycan.
 Native heparin is a polymer with a molecular
weight ranging from 3 kDa to 50 kDa,
 although the average molecular weight of
most commercial heparin preparations is in
the range of 12 kDa to 15 kDa.
Gihan Gawish.Dr
Heparin structure
 Heparin
is
a
member
of
the
glycosaminoglycan family of carbohydrates
(which includes the closely-related molecule
heparan sulfate) and consists of a variablysulfated repeating disaccharide unit.
Gihan Gawish.Dr
Most of the amino groups of glucoseamine
carry an N- sulphate group, a small fraction
carry n-acetyl group
A heptasaccharide fragment of heparin
Gihan Gawish.Dr
Gihan Gawish.Dr
Composition
 Cartilage is a type of dense connective tissue.
 It is composed
chondrocytes
of
specialized
cells
called
 that produce a large amount of extracellular
matrix composed of collagen fibers,
 abundant ground substance rich in proteoglycan,
and elastin fibers.
 Cartilage is classified in three types, which differ
in the relative amounts of these three main
components.
Gihan
Gawish.Dr
Occurrence
 Cartilage is found in many places in the
body including the articular surface of the
bones, the rib cage, the ear, the nose, the
bronchial tubes and the intervertebral discs.
 Its mechanical properties are intermediate
between bone and dense connective tissue
like tendon.
Gihan Gawish.Dr
Types of cartilage
1. Hyaline cartilage
 It is a rather hard, translucent material rich in
collagen and proteoglycan.
 It covers the end of bones to form the smooth
articular surface of joints.
 It is also found in the nose, the larynx and
between the ribs and the sternum.
 Bones grow via a hyaline cartilage intermediate, a
process called endochondral ossification.
Gihan Gawish.Dr
2. Elastic cartilage
 It contains large amounts of elastic fibers
(elastin) scattered throughout the matrix.
 It is stiff yet elastic, and is important to
prevent tubular structures from collapsing.
 Elastic cartilage is found in the pinna of the
ear, in tubular structures such as the
auditory (Eustachian) tubes and in the
epiglottis.
Gihan Gawish.Dr
3. Fibrocartilage
 It is the most common form of cartilage by weight.
It is characterized by a dense network of Type I
collagen.
 It is a white, very tough material that provides high
tensile strength and support.
 It contains more collagen and less proteoglycan
than hyaline cartilage. Thus, its properties are
closer to those of tendon than hyaline cartilage.
 It is present in areas most subject to frequent
stress like intervertebral discs, the symphysis
pubis and the attachments of certain tendons and
Gihan
Gawish.Dr
ligaments.
Section through the
head of the femur
Gihan Gawish.Dr
Composition
 The primary tissue of bone, osseous tissue, is a
relatively hard and lightweight composite material,
 Osseous tissue formed mostly of calcium
phosphate in the chemical arrangement termed
calcium hydroxylapatite Ca5(PO4)3(OH) (this is
the osseous tissue that gives bones their rigidity).
 It has relatively high compressive strength but
poor tensile strength, meaning it resists pushing
forces well, but not pulling forces.
Gihan Gawish.Dr
 While bone is essentially brittle, it does have
a significant degree of elasticity, contributed
chiefly by collagen.
 All bones consist of living cells embedded in
the mineralized organic matrix that makes
up the osseous tissue.
Gihan Gawish.Dr
Molecular structure of bones
1. Matrix
 The matrix is the major constituent of bone,
surrounding the cells.
 It has inorganic and organic parts.
Gihan Gawish.Dr
1-1 Inorganic
 The inorganic is mainly crystalline mineral salts
and calcium, which is present in the form of
hydroxyapatite.
 The matrix is initially laid down as unmineralised
osteoid (manufactured by osteoblasts).
 Mineralization involves osteoblasts secreting
vesicles containing alkaline phosphatase.
 The vesicles then rupture and act as a centre for
crystals to grow on.
Gihan Gawish.Dr
1-2 Organic
 The organic part of matrix is mainly composed of
Type I collagen.
 The organic part is also composed of various
growth factors, the functions of which are not fully
known.
 These
factors
present
include
glycosaminoglycans, osteocalcin, osteonectin,
bone sialo protein and Cell Attachment Factor.
Gihan Gawish.Dr
Bones act as reserves of minerals important
for the body, most notably calcium and
phosphorus
Calcium balance
 The process of bone resorption by the osteoclasts
releases stored calcium into the systemic
circulation and is an important process in
regulating calcium balance.
 As bone formation actively fixes circulating
calcium in its mineral form, removing it from the
bloodstream, resorption actively unfixes it thereby
increasing circulating calcium levels. These
processes occur in tandem at site-specific
locations.
Gihan Gawish.Dr
The role of bone in calcium
metabolism
 Although calcium flow to and from the bone is neutral,
about 5 mmol is turned over a day.
 Bone serves as an important storage point for calcium, as
it contains 99% of the total body calcium.
 Calcium release from bone is regulated by parathyroid
hormone.
 Calcitonin stimulates incorporation of calcium in bone,
although this process is largely independent of calcitonin.
Gihan Gawish.Dr
Major Mediators of Calcium and
Phosphate Balance
 Parathyroid hormone (PTH)
 Calcitriol (active form of vitamin D3)
Gihan Gawish.Dr
Role of PTH





Stimulates renal reabsorption of calcium
Inhibits renal reabsorption of phosphate
Stimulates bone resorption
Inhibits bone formation and mineralization
Stimulates synthesis of calcitriol
Net effect of PTH 
Gihan Gawish.Dr
↑ serum calcium
↓ serum phosphate
Regulation of PTH
Low serum [Ca+2]  Increased PTH secretion
High serum [Ca+2]  Decreased PTH secretion
Gihan Gawish.Dr
Role of Calcitriol
 Stimulates GI absorption of both calcium
and phosphate
 Stimulates renal reabsorption of both
calcium and phosphate
 Stimulates bone resorption
Net effect of calcitriol 
Gihan Gawish.Dr
↑ serum calcium
↑ serum phosphate
Overview of Calcium-Phosphate Regulation
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Overview of Calcium Balance
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Overview of Phosphate Balance
Gihan Gawish.Dr
Gihan Gawish.Dr
PERIODONTIUM
Cementum
Pulp cavity
Enamel
Dentin
Gingiva
PDL
Alveolar bone
Cementum
Sharpey's fibers
Attachment
organ
Periodontal
ligament
Root canal
Alveolar bone
Apical foramen
Gihan Gawish.Dr
Alveolar vessels
& nerves
Structure:
 The basic tissues
that make up the
vertebrate tooth are
enamel,
dentin,
cementum, and pulp
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1.Enamel
 Enamel is the hardest tissue in the body because of
the very high concentration, about 96%, of mineral
salts.
 The remaining 4% is water and organic matter.
 The protein is in embryonic enamel is a fibrous
protein characterized by a very high proline content
and presence of hydroxyproline that is laid down
and calcified.
Gihan Gawish.Dr
 The enamel has no nerve supply, although it
is nourished to a very slight degree from the
dentin it surrounds.
 The fine, microscopic hexagonal crystallites
rods (prisms) of apatite which make up the
enamel are held together by a cementing
substance.
Gihan Gawish.Dr
2.Dentin
 Dentin, a very bonelike tissue, makes up the
bulk of a tooth, consisting of
1. 70% of such inorganic material as calcium and
phosphorus ,
2. and 30% of water and organic matter, principally
collagen.
 The rich nerve supply makes dentin a highly
sensitive tissue.
Gihan Gawish.Dr
3. Cementum
 Cement is a calcified tissue, a type of
modified bone less hard than dentin
1. It is approximately 45% inorganic material
(mainly hydroxyapatite),
2. 33% organic material (mainly collagen)
3. and 22% water.
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 Cementum is excreted by cementoblasts
 The principal role of cementum is to serve
as a medium by which the periodontal
ligaments can attach to the tooth for stability.
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Role of Cementum
1) It covers and protects the root dentin
(covers the opening of dentinal tubules)
2) It provides attachment of the
periodontal fibers
3) It reverses tooth resorption
Gihan Gawish.Dr
Cementum simulates bone
 Organic fibrous framework, ground
substance, crystal type, development
Cellular component
 Incremental lines (also known as
“resting”
lines; they are produced
by continuous but phasic,
deposition of cementum)
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Differences between cementum and
bone
• Not vascularized – a reason for it being resistant
to resorption
•More resistant to resorption compared to bone
•Lacks neural component – so no pain
• 70% of bone is made by inorganic salts
(cementum only 45-50%)
Gihan Gawish.Dr
4. Pulp
 The dental pulp is the central part of the tooth filled with
soft connective tissue.
 This tissue contains blood vessels and nerves that along
the border between the dentin and the pulp are
odontoblasts, which initiate the formation of dentin
 Other cells in the pulp include fibroblasts, preodontoblasts,
macrophages and T lymphocytes
 The pulp is commonly called "the nerve" of the tooth.
Gihan Gawish.Dr
Dental caries
 Tooth decay, which is also called dental cavities or
dental caries, is the destruction of the outer surface
(enamel) of a tooth.
 Decay results from the action of bacteria that live in
plaque, which is a sticky, whitish film formed by a
protein in saliva (mucin) and sugary substances in
the mouth.
 The plaque bacteria sticking to tooth enamel use
the sugar and starch from food particles in the
mouth to produce acid.
Gihan Gawish.Dr
The transitions from sound tooth structure to
caries-affected tooth structure to cariesinfected tooth structure.
Plaque with
refined carbohydrate
Sound
tooth
structure
Demineralization
Remineralization
Removal of plaque,
saliva, fluoride,
reduced carbohydrates
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Carious
tooth
(affected)
Demineralization
Carious
tooth
(infected)
Irreversible destruction
requiring restorative dentistry
to replace lost structures
 The most effective and least expensive means of
rendering the tooth less susceptible to the caries
attack is through fluoridation ,either by systemic
means such as water fluoridation, or by topical
application of fluoride to the tooth surfaces.
 Water fluoridation (approximately 1 part per
million) by itself reduces the incidence of caries by
50–60%.
 Topical fluoridation can be instituted by many
means, ranging from professional applications in
the dental office to self-applied fluoride in the form
of toothpastes, mouth rinses, and gels
Gihan Gawish.Dr
 It is believed that fluoride, when incorporated into
the mineral phase of enamel and the other hard
tissues, results in a better crystalline structure that
is less susceptible to acid dissolution.
 Alternatively, the anticaries effect of fluoride may
be due to its ability to inhibit demineralization and
promote remineralization .
Gihan Gawish.Dr
 Florid has antimicrobial activity which inhibits
the
enzymatic
production
of
glucosyl
transferase
Glucose glucosyltransferaseextra cellular polysaccharides
 polysaccharides increases bacterial adhesion
Gihan Gawish.Dr