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CONNECTIVE TISSUES
CONTENT
INTRODUCTION
CLASSIFICATION
- Connective tissue proper
CELLS IN CONNECTIVE TISSUES
- Fibroblasts
-Macrophages
-Adipose cells
- Mast ells
TYPES OF FIBERS
- Collagen fibers
- Reticular fibers
- Elastic fibers
GROUND SUBSTANCE
- Proteoglycans
- Glyoproteins
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INTRODUCTION
These are group of tissues predominantly composed of intercellular material
(matrix). They are derived from the mesoderm. Connective tissues play many
important roles in the body both structural and defensive.
Early during embryological development the ectoderm and endoderm become
separated by the third germ layer the Mesoderm. The tissues formed by this layer is
called Mesenchyme mesos means middle and enchyma means infusion.
Connective tissue consists of cells and a extra cellular matrix that includes
extracellular fibers, substance and tissue fluids.
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CLASSIFICATION OF CONNECTIVE TISSUES
Classification depends upon
composition organ ization of the cellular and extra cellular components
special functions
CONNECTIVE TISSUE PROPER
Loose connective tissue
Dense connective tissue
-Irregular-Regular
SPECIALIZED CONNECTIVE TISSUE
Adipose tissue
Blood
Bone
Cartilage
Hemopoietic tissue
Lymphatic tissue
EMBRYONIC CONNECTIVE TISSUE
Mesenchyme
Mucous connective tissue
Connective Tissues Proper has two sub types:-
Loose connective tissue
Dense connective tissue
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Loose Connective Tissue or Areolar Tissue
These cells are characterized by loosely arranged fibers, abundance of cells, thin
and relatively sparse, viscous gel like consistency..
Dense Connective Tissue
On bases of arrangement of fibers it is further sub divided as: -
Dense Irregu lar Connective Tissue
Dense Regular Connective Tissue
Dense Irregular Connective Tissue
These are found in the region which experience mechanical stress and where
protection is to be provided. Contain high proportion of collagen which forms thick
bundles oriented in yarious directions. Due to high proportion of collagenous fibers it
provides high strength. Cell population is less and is typically of a single type
fibroblast. Active fibroblast are few. Mostly are flattened with heterochromatic nuclei.
Found in dermis, connective tissue sheaths of muscle, nerve and large blood
vessels.
Dense Regular Connective Tissue
These are characteri zed by ordered and densely packed array of fibers and cells.
These are the main functional component of tendons, ligaments and aponeuroses.
Tendons
They are cord like structure that join muscle to bone. It consists of parallel bundles of
collagenous fiber between which are row of fibroblast present. The substance of
tendon is surrounded by a thin connective ti ssue capsule epitendineum.
Ligament
These are similar to tendon. They consist of fibers and fibrob last arranged parallel
direction. The fibers are less regularly arranged as compared to that of tendon
function of ligament is to join bone to bone.
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Aponeuroses
They are much more like flattened tendon. The fibers are arranged in multiple layers.
These are sheet of dense connective tissue. It bears tensile forces directly or
indirectly from skeletal muscle to other muscle cartilage or bone. The bundles of
collagen fibers in a layer are arranged at 90 degree to neighboring layers.
CELLS PRESENT IN CONNECTIVE TISSUES
Connective tissue cells can be classified as:-
Fixed
Wandering
Fixed
These cells are relatively stable permanent residents of the tissue. These cells are: -
Fibroblasts
Macrophages
Adipose cells
Mast cells
Wandering
They migrate into tissue from blood on response to specific stimuli. These cells are:-
Lymphocytes
Monocytes
Neutrophils
Eosinophils
Basophils
Plasma cells
FIBROBLAST
These are the principal cells of connective tissue. They are responsible for the
synthesis of collagen, elastin and reticular fibers and the complex carbohydrates of
the ground substance. Its structure is flattened, irregular in outline having branching
processes.
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Profile is spindle shaped. Active fibroblast has an oval, pale-staining nucleus and
has more cytoplasm. Nucleus of active fibroblast is euchromatic (opened - faced).
Old fibroblasts are elongated with less cytoplasm. Nucleus of old, inactive fibroblast
is flattened, heterochromatic (closed - faced). Fibroblasts are separated from one
another by extracellular matrix components. Exception is embryonic tissue and
periodontal ligament were there is cell to cell contact. Originate from mesenchymal
cells. Once they are differentiated they are replicate by mitosis. Cultured fibroblast
undergoes 50-55 division.
Fibroblast from long Iived species divides more then fibroblast from short lived
species. Gradual loss of telomere DNA is the onset of senescence. Accumulation of
oxidative damage to DNA & protein contribute to senescence. Cultured fibroblasts
that become senescent never die.
MACROPHAGES
A.lso known as Histiocytes or Clasmatocytes
These ells are relative ly larger in size 15 - 20 11m diameter. Nuclei are usually
indented or kidney shaped. Cytoplasm is mildly basophilic and typically has a "frothy"
appearance under light microscope. Surface of macrophages have numerous folds
and fingers like projection. These folds and fingers helps in Phagocytosis
ADIPOSE CELLS
When occurring singly the cells are oval Qr spherical in shape, but when mutually
compressed they become Polygonal in shape. Each cell consists of peripheral rim of
cytoplasm, in which the nucleus is embedded surrounding a single large central
globule of- fat. They are fixed and stained by osmium tetroxide and specially
coloured by alcoholic solution of certain dyes - sudan III, sudan black. Adipose cells
when acumulated in large number are called Adipose tissue.
MAST CELLS
Also known as Mastocytes or Histaminocytes. These cells are important defensive
cells. Their shapes are round or oval about 12 micro meter in diameter. It has many
Filopodia extending from cell surface. It's cytoplasm is filled with large granules. It
has a centrally placed nucleus. It is stained by Periodic Acid Schiff PAS) method.
Mast cells are distributed in vicinity of small blood vessels.
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TYPES OF FIBERS
Each fiber type is produced by the fibroblast. They are composed of protein
formed by long peptide chains
Fibers are mainly of three types:
Collagen fibers
Reticular fibers
Elastic fibers
Collagen Fibers
It forms the most abundant fibers of connective tissue. They are very flexible,
have high tensile strength. Provide strength and support to the tissue. Appear as
wavy structures of variabIe width and indeterminate length. They stain readily with
eosin and other acid dyes. Linder electron microscope they appear as bundle or
bundles of fine thread like subunit called collagen fibril. Collagen fibrils within a fiber
are relatively of uniform in length. Developing or immature tissue fibrils are as small
as 15-20 nm in diameter fibrils of dense regular connective tissue like tendon
measure up to 200nm in diameter.
They constitute the most abundant protein found in the body. Collagen family
consists of 30 different genes. This produces 19 known collagens. They are
composed of 3 polypeptide alpha chains coiled around each other. This forms a
typical collagen triple - heIix configuration. They include the presence of amino. acid
glycin in every third position. Collagen molecules are called tropocollagen. They are
300nm long and 1.5nm in thickness. They exhibit a sequence of closely spaced
transverse band. These repeat after every 68nm along the length of the fibril.
Variation among collagens includes :-
Difference in the assembly of the basic polypeptide chains. Different length of
triple helix. Interruption in the helix and difference in the terminations of the helical
domains. Sylthesis of collagen involves both event that occur Within and outside the
fibroblast. Within the fibroblast precursor of collagen is formed called procollagen.
The actual collagen is formed outside the fibroblast. Involving enzymatic activity at
the plasma membrane. Collagen molecules formed are aliened to form fibril under
the guidance of ceII.
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INTRACELLULAR EVENTS
First cleavage of polypeptide chain occurs. Then hydroxylation of proline and
lysine takes place. Addition of O-linked sugar group to some ofthe hydroxylysine
residues and N-linked sugar to the terminal ends take place. Formation of triple
helix by 3 polypeptide chains except at the terminals occurs. Then Formation of
interchain and intrachain hydrogen bonds that influence the shape of the molecule.
Now the resultant molecule is called procollagen. Procollagen moves out of cell by
exocytosis of secretory vesicles.
EXTRACELLULAR EVENTS
Firstly procallagen is converted to collagen by procollagen pentidase. Then
the secreted molecules concentrate at an indentation on the cell surface. Then
assemble in row occurs to cross link.
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TYPE OF COLLAGEN
TYPES COMPOSITION LOCATION FUNCTION
I -1, -2 Skin,bone,dentin,
cementum,
tendon,ligament
Resistance to
force, tension,
stress
II -1 Cartilage,
intervertebral disk
Tensile strength to
connective tissue
III -1 Embryonic
connective tissue,
pulp,skin,bloodvessels
Tensile strength to
connective tissue
IV -1, -2, -3, -4,
-5, -6
Basement
membrane
Structural network
of basement
membrane
V -1, -2, -3 Basement
membrane,blood
vessel, ligament,
dentin,periodontal
tissue
Provides tensile
strength
VI -1, -2, -3 Ligament, skin,
cartilage
Bridging between
cells and matrix
VII -1 Epithelium
(skin,mucosa)
Strengthens
epithelial-
connective tissue
junction
VIII -1, -2 Cornea Tissue support
IX -1, -2, -3 Cartilage, vitreous
humor
Attaches functional
group to surface of
type II fibril
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X -1 Hypertrophic zone
of cartilage growth
plate
Calcium binding
XI -1, -2 Cartilage, vitreous
humor
Provides tensile
strength
XII -1 Widespread in
connective tissue
Modulates fibril
interactions
XIII -1 Cell surface, focal
adhesions,
intercalated disks
Cell-matrix, cell-
cell adhesion
XIV -1 Widespread in
connective tissue
Modulate fibril
interaction
XV -1 Endothelial
basement
membrane
Proteolytic release
of antiangiogenic
factor
XVI -1 Endothelialmuscle,basement
membrane
unknown
XVII -1 hemidesmosomes Cell attachment to
matrix
XVIII -1 Endothelial
basement
membrane
unknown
XIX -1 Endothelial
muscle,basement
membrane
unknown
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INHERITED DISEASES INVOLVING COLLAGENS
I. Osteogenisis imperfecta or brittle bone diseases due to deficiency of Type I
2. Ehlers Danlos syndrome (hyper extensible skin, hyper mobile joint and
tissue
fragility) due to defi ciency of Type I, III,Y
3. Stickler syndrome retinal detachment, cataract, hearing loss, joint problem,
cleft
palate, facial and dental abnormalities) due to deficiency of Type II, XI
4. Epidermolysis bullosa (separation of epidermis and dermis) due to
deficiency of
Type VII, XVII
RETICULAR FIBERS
It provides supporting framework for cellular constituents of various tissues
and organs of the body. They are arranged in mesh like pattern or network. They are
closely related to collagen fibers as it also contains collagen fibrils. They are
composed of Type III c0l1agen. Type IV may be also associated. They do not bundle
to form thick fibers. Found at the boundary of loose connective tissue. They are also
present as a supporting stroma in hemopoietic and lymphatic tissues. These type of
reticular fibers are produced by special cells call ed reticular cells. Rest all reticular
fibers are produced by fibroblast.
ELASTIC FIBERS
Elastic fibers provide tissues with the ability to respond to stretch and
distension. They are typically thinner then collagen fibers. They are arranged in
branching pattern forming a three dimensional network. Fibers are interwoven with
collagen fibers this prevent tearing from excessive stretching. They are produced by
fibroblast and smooth muscle cells.
Elastin
It's a protein that is rich in proline and glycine but poor in hydroxyproline and
completely lacks hydroxylysine. Microfibril are a fibular glycoprotein that is relatively
straight and thin measuring 12 nm in diameter. They are found in ligament vertebral
column and neck and vocal cord.
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GROUND SUBSTANCE OR INTERFIBULLAR SUBSTANCE
It is the component that occupies the space between the cells and fibers. It is
a colourless transparent substance. It is viscous clear substance having a slippery
feel. it has high water content. It provides mechanism for regulating tissue water
content & diffusion of nutrition, waste and other molecules. Physical properties of
ground substance are same whether viscous nature in connective tissue or turgid
character in cartilage. It is stained by periodic acid schiff (PAS) method. In routine
H&E preparation ground substance is always lost due to extraction during fixation
and dehydration. Functions as a molecular sieve through which nutrients diffuse
between blood capillaries and cells.
Glycosaminoglycan is a major component.
GLYCOSAMINOGLYCANS (GAG)
these are unbranched chain of repeating disaccharide units. Each unit carry
one or more negatively charged group. This negative charge helps in osmotic
activity. Due to high water attraction it forms hydrated gel. This causes swelling
pressure and helps in keeping fibriIs apart and causes stiffness. On the basis of
Specific sugar residues, Nature of linkages and Degree of sulfation
Glycosaminoglycans are of seven distinct types.
1. Hyaluronic acid
2.Chondroitin sulfate
3. Dermatan sulfate
5. Heparin
6. Keratan sulphate
HYALURONIC ACID
These are found in abundance in embryonic tissues and cartilage also found
in all ECM. It has simple structure of extremely long chains of non-sulfated
disaccharides. It forms. The keystone in aggregation of proteoglycans and link
protein. Found in abundance in embryonic tissues and catilage also found in all extra
cellular matrix. It has a simple struture of extremely long chains of non-sulfated
disaccharides. It forms the keystone in aggregation of proteoglycans and link protein.
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Hyaluronic acid is not bound to core protein and other glycosaminoglycans are
bound to the core protein forming a bottle like structure.
CHONDROITIN SULPHATES 4 & 6 (CS4, CS6)
They are labeled as according to the predominant component sulphate (4 &
6). Found in cartilage in very high concentration and in most extra cellular matrix.
Most are mixed or hybrid AGAGs. Undersulphated chondroitinsulphates is CS4
found in cornea. While properly sulphated chondroitin sulphates is CS6 are found in
vitreous body and oversulphated chondroitin sulphates is CSO which are found in
cartilage of fishes.
KERATAN SULPHATES (KS)
Their polymer back bone is identical to that of chondroitin. They are Present in
age cartilage and intervertibral discs and cornea.
DERMA SULPHATES (DS)
They are formed by CS4. OS aggregates with itself in solution, this causes the
organization of most extra cellular matrix. They are found in very high concentration
in tissue.
HEPARAN SULPHATES
It is a important constituent of basement membrane. They interact directly
with constituents of extra cellular matrix. They are usually located on skin fibroblast.
HEPARIN
They are made-up of repeating disaccharide units contains glucosamine and
two uronic acids. They are usually located in mast cells, liver lung and skin.
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GLYCOPROTEIN
There may be one or more carbohydrate chains covalently linked to a protein.
The chains may be neutral or negatively charged. They are frequently branched.
They have a acihesivc properties. One of their primary function is to bind cells to
extracellular matrix elements.
SOME FUNCTIONS OF GLYCOPROTEIN AND PROTEOGLYCANS
They act as structural component of the extra cellular matrix. They have
specific infraction with collagen, elastin, fibronectin and laminin. They facilitates cell
migration. Thay play a role in making cartilage stress bearing. They acts as
anticoagu lant. They are components of plasma membrane where they may act as
receptors and participate in cell adhesion.
FILAMENTOUS PROTEIN WITH ADHESIVE PROPERTIES
These are structural proteins, which contains molecules that mediate
adhesion between cells and extra cellular matrix. These are glycoproteins, which
helps cell to adhere at the appropriate matrix structure. They contain signaling
molecules which are detected by the cell surface receptors. They initiates changes
within the cytoplasm. The best known filamentous proteins are Fibronectin, Laminin
and Tenascin.
FINRONECTIN
Larce glycoprotein molecule consisting of a dimer held together by disulphide
link. Each subunit is composed of a string of large repetitive domain joined by flexible
region. These bears binding sites for collagen and cell surface receptors. They are
bound in onkrly fashion to cell su rface forming fibronectin filaments.
FIBRONEXUS
It is the term use to describe the morphologic relationship between
Intracellular filament, Cell membrane, Extracellular filament and to the sticky
attachment glycoprotein fibronectin. The binding of myofibroblast to each other
causes fibronexus to transmit the collective forces generated by the contraction of
actin microfilaments throughout the granulation tissue. This causes wound
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contraction. Fibronexus are associated with fibroblast in transseptal fiber region of
gingiva. New studies show fibronexus are present only in inflamed gingiva.
LAMININ
Large flexible cruciform molecule composed of three polypeptide chains (a,
13, y). Their terminal two third are wound round each other to form the stem of cross.
The free end forms the upright members and transverse members. It bears binding
sites for a number of extra cellular matrix molecules like heparan sulphate, Type IV
collagen, and laminin.
TENASCIN
Large glycoprotein consisting of six subunits joined at one end to form a
radiating structure which resembles spoke of a wheel. It is abundant in embryonic
tissues. These are fo und less in adult tissues. They play important role in guiding
cell migration.
Tenascin is a glycoprotein associated with the extra-cellular matrix and the
surface of some cell types. During early stages of neural crest migration, tenascin is
observed in a dense matrix surrounding premigratory cranial neural crest cells.
During advanced neural crP-:t migration, tenasc in immunoreactivity colocaUzed with
and appeared to be on the surface of migrating neural crest cells. At later stages;
tenascin is present around the otic vesicles, retina, lens, and in an interstitial matrix
in the region ofthe branchial arches. At the level of the occipital somites, tenascin
immunoreactivity is present around the neural tube, notochord and on the basal
surface of the ectoderm. Tenascin is requ ired for proper cranial neural crest
migration.
PROTEOGLYCANS
These are very large macromolecules of protein to which many
glyscosaminoglycans molecules are covalently bounded. Proteoglycan binds growth
factors and cytokines. They are essential co-receptor for growth factor and are
involved in transmembrane signaling. Five proteoglycan are of particular interest
these are Decorin, Versican, Perlecan, Syndecan and CD44.
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DECORIN
They are called so because it binds to collagen and is visualized as
"decoration" on collagtn fibril. They play an important role in regu lation of growth,
diameter or both of collagn fibril.
VERSICAN
They are large proteoglycan that assist in bonding cell surface glycoprotein to
extra cellular matrix.
PERLECAN
They are cell surface proteoglycan. Its name arises because the large core
protein containing number of globular domains which form pearl necklace like
structure. Itbinds fibroncctin that helps in anchoring fibroblast to extra cellular matrix.
SYNDECAN
Ithas an extracellular domain, membrane-spanning domain and cytoplasmic
domain. It binel collagen and other extracellular glycoproteins.
CD44
It has transmembrane structure which is capable of binding to fibronectin,
laminin and collgen.
CLASSIFICATION OF PROTEOGYCANS
According to the shape and size of the protein core Proteoglycans are
classified into 3 groups: -
I. Small
2. Large
3. Very large
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SMALL PROTEOGLYCANS
They are attached to the family of globular protein of very small size amino
acid and
gene structure. Electron microscopically they appears as Tadpole - shaped with
globular protein at the head and one or two glycan chains at the tail.
LARGE PROTEOGLYCANS
Their molecule contains one or two globular protein domains. They are
connected via a polypeptide chain. To which 5 - 10 acidglycosaminoglycans are
attached.
VERY LARGE PROTEOGLYCANS
These are complex molecules with up to three globular regions linked by a
polypeptide chain. To which about 100 chondroitin sulphates and keratan sulphates
chains are attached.
PROTEOGLYCANS COLLAGEN INTERACTIONS
The proteogylcans interact with collagen rich fibril s. They sometimes
completely encircle them. Very frequently they form bridge between neighboring
fibrils. In cornea as many as 4 tibil s are bridged by the same filament of
acidglycosaminoglycans. They acts as cross linking structure between proteoglycan
cores which are attached to the collagen fibril.
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BIBLIOGRAPHY
Gray's Anatomy - Churchill Livingstone, 38th edition. Oral Histology Development, Structure And Fundamental - A. R. Ten Cate,
5th & 6TH edition.
Histology A Text And Atlas - Michael H. Ross Lynn J. Romrell, Gordon I.
Kaye, 3rd edition.
Bloom & Fawcett's Concise Histology - Don W. Fawcett & Ronald P. lenish,
2nd edition
Di Fiore's Atlas ofHistology With Functional Correlations - Victor P.
Eroschenko, 7th edition
The Periodontal Ligament in Health & Disease - Barry K. B. Berkovitz,
Bernard. J. Moxham, 2nd edition
Harper's Biochemistry - Robert K. Murray, Daryl K. Granner, Peter A. Mayes,
VictorW. Rodwell, 24th edition.
Journal of Neuroscience Research Volume 21 , Issue 2-4 , Pages 135 - 147
Published Online: 11 Oct 2004.