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7/28/2019 Connect Tissue

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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.

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