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CONNECTIVE TISSUE I

DENTAL MICROSCOPIC ANATOMY December 2007.


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CONNECTIVE TISSUE COMPOSITION

CELLS: fibroblastsimmune

vascular

EXTRACELLULAR

MATRIX (ECM):

Fibers - collagen

elastic

reticular

Ground substance -

glycosaminoglycans

proteoglycans

adhesive proteins

Tissue fluid


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MAJOR TYPES OF CONNECTIVE TISSUE

Cell

LOOSE CONNECTIVETISSUE

Collagenfiber

Other

fibers

Fatdroplets

BLOOD

WBC

Plasma

DENSE CONNECTIVETISSUE

Cell

nucleus

Collagenfibers

CARTILAGE

BONE

Matrix

Cell

RBC

Matrix

Cell

PROPER ANDSPECIALISED

ADIPOSE TISSUE


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CONNECTIVE TISSUE FUNCTIONS

Structural support

Hard connective tissuesSoft connective tissues

Energy storage

Adipose tissue Medium for exchange

Tissue fluid

Avascular tissue support

Defense and protection

Inflammatory response

Immune response

Wound repair


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LOOSE C.T. more cells, less collagenIntestinal villi Lamina propria in villus

Mesentery(whole mount,

Verhoeff

Hematoxylin stain)


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DENSE C.T. more collagen, less cells

DENSE IRREGULAR

C.T. IN DERMIS

(collagen fibers less

oriented)

DENSE REGULAR

C.T. IN TENDON

(collagen fibers more

oriented)


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Resident (or fixed) cells- reside in CT

Fibroblast (including reticular cells)

Adipocyte

Macrophage (differentiates from monocyte)

Mast cell

Plasma cell (differentiates from B lymphocyte)Undifferentiated cell (mesenchymal cell)

Transient (or wandering) cells- migrate into CT

NeutrophilEosinophil

Basophil all blood cells

Lymphocyte

Monocyte

CONNECTIVE TISSUE CELLS


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RESIDENT CELLS

Derived from mesenchyme live and die where they were born

not CT cells

fibroblast

adipocytechondroblast

chondrocytes

Undifferentiatedmesenchymal cell

osteocyte

osteoblastmesothelial

cell

endothelialcell


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Transient and some resident cells arise from precursor cells

that develop in the bone marrow

TRANSIENT CELLS

B lymphocyte

Monocyte

basophil

eosinophil

neutrophil

red blood cells

Hemopoietic stem cell

macrophage

megakaryocyteosteoclast

mast cellPlasma cell


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FIBROBLASTS

Fibroblast Fibrocyte

Fibroblasts in dense irregular CTFibroblasts in loose CT

Tendinocytes


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Predominant cell of connective tissue that manufactures the

precursors of the extracellular environment (proteins of

fibers and ground substance)

Fusiform cell with many cytoplasmic processes, light

cytoplasm, large ovoid euchromatic nucleus and prominent

nucleolus (active)

Inactive cells (fibrocytes) are smaller with darker elongate

nuclei and acidophilic cytoplasm hard to distinguish from

matrix they have already synthesized.

In wound healing can become myofibroblasts whose

contraction helps wound closure after injury.

Synthesize and secrete growth factors (e.g. FGFs) which

influence growth and differentiation of neighbouring cells.

FIBROBLASTS


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Unilocular - one huge lipid droplet displaces nucleus and cytoplasm to

side of cell (droplet has no membrane); present as individual cells, small

groups of cells, or as large accumulations in white adipose tissue

Multilocular less abundant, smaller cells with many lipid droplets and

many mitochondria containing thermogenin - promotes release of

energy as heat; present in brown fat (thermogenesis)

Specialised for the store and release of energy, well vascularized

ADIPOCYTES

W

B


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Fatty acids in CT diffuse into adipocytes and are esterified to

form triglycerides that form the lipid droplet

FAT STORAGE IN ADIPOCYTES


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Large cell (20-30 m) with many cytoplasmic granules whichcontain: histamine, growth and inflammatory factors, heparin, andother enzymes and proteins

Granule release - triggered by antigens, causes increase in

permeability of small blood vessels and constriction of bronchioles

Originate from bone marrow precursor

LM EM

MAST CELLS


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MACROPHAGES

Originate in bone marrow, circulate as monocytes, becomemacrophages when migrate into tissues

Large irregularly-shaped cells, indented nucleus, numerous

cytoplasmic vesicles, lysosomes and phagosomes

Phagocytose and destroy dead cells and other foreign material

Present antigens to plasma cells for antibody production


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Arise from B lymphocytes

Large eccentric heterochromatic cartwheel nucleus

Basophilic cytoplasm and prominent negative Golgi

Synthesize and secrete antibodies

PLASMA CELLS

LM EM


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COLLAGEN FIBERS

Composed of fiber-forming collagen proteinsType I collagen fibers found in loose and dense CT

Some collagen proteins do not form fibers

Fibers do not branch

RETICULAR FIBERS

Composed of type III collagen

Form loose mesh-like network of fibers

Do not form thick bundles of fibers

CONNECTIVE TISSUE FIBERS

ELASTIC FIBERS

Composed of elastin and fibrillin proteins

Fibers are thinner than collagen fibers & may branch

Elastic fibers are deformable (can stretch and recoil)


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Collagen fibers Reticular fibers Elastic lamellae

(tendon) (adrenal cortex) (aortic wall)

CONNECTIVE TISSUE FIBERS


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COLLAGEN FIBERS

tendon

muscle

fiber

fibril

bundle

Overlappingregion Gap region

Tropocollagentriple helix

Most abundant type of

connective tissue fiber. Fibers are flexible,

unbranched and have ver

high tensile strength (>

stainless steel)

Collagen fibers consist of

bundles of threadlike

fibrils bound together by

non-fibrillar collagen andproteoglycans

Fibrils are composed of

arrays oftropocollagen

building blocks.


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COLLAGEN FIBERS

Fiberscan see under LM, usually >100 m long and ~0.5-5 m in

diameter, may be oriented in different directions for strength (e.g.

dermis) or highly organized (e.g. cornea transparent). Fibers arecomposed of bundles of longfibrils,usually of similar diameters.

Fibrils10-300 nm in diameter (depending upon tensile load). Exhibit

banding that repeats every ~68 nm (EM).Fibrilsare made from

tropocollagenmolecules that assemble head to tail and side to side

(staggered), extracellularly.

TROPOCOLLAGEN


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Tropocollagen - three chains (sameor different) intertwined to form a triple

helix (right)

~ 25 different chains (~1000 a.a. long)are encoded by different genes

chains consist of repeating amino acidtriplets: Gly-X-Y (left). X & Y arecommonly proline, hydroxyproline or

hydroxylysine

Every third a.a. must be glycine to fit in

triple helix. Rings in proline andhydroxyproline stiffen chains

Fibrous (fiber-forming) collagen chains form one long triple helix

TROPOCOLLAGEN


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1. Transcription of collagen genes,

translation of chain mRNA on rER,translocation of preprocollagen into

rER lumen, removal of signal peptide to

yield procollagen with propeptides at N-

and C-termini

2. Hydroxylation (circles) of selected

prolines and lysines by peptidyl proline

(or lysine) hydroxylase

3. Glycosylation (triangles) of selectedhydroxylysine

4. Assembly of 3 chains into 1 pro-collagen triple helix via registration

peptides

1.

2.

3.

4.

FORMATION OF PROCOLLAGEN

MODIFICATION AND


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MODIFICATION AND

SECRETION OF PROCOLLAGEN4. Self-assembly of 3 chains into 1

procollagen triple helix

5. Transport through Golgiapparatus (where oligo-saccharides are added) and

secretion (not shown:hydroxylation and glycosylationof chains; secretory vesicles)

6. Extracellular cleavage (arrows)

of propeptide by procollagenpeptidases to form maturetropocollagen

7. Self-assembly of tropocollagen

into fibrils in fibroblast "coves"

6.

5.

4.

7.

COLLAGEN FIBRIL ASSEMBLY


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Cove - promotes fibril formation by increasing

the local concentration of tropocollagen molecules

COLLAGEN FIBRIL ASSEMBLY

IN COVES

COVE

COLLAGEN CROSS LINKAGE AND


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Collagen is stabilized by

intra- and inter- molecularcovalent cross-linking of

tropocollagens involving

lysine and hydroxylysine

residues, catalyzed by lysyloxidase.

68nM periodicity is due to

staggered cross linking

between residues near theamino terminal of one

tropocollagen and the

carboxyl terminal of anothe

in the adjacent row.

COLLAGEN CROSS LINKAGE ANDFIBRIL STRIATIONS

Type Form Tissue Synthesizing Cells


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Collagen Types

Type Form Tissue Synthesizing Cells

I fibril, largebanded fiber

bone, skin, tendons, ligaments, cornea,internal organs

(~90% of body collagen)

fibroblast, osteoblast

II fibril, smallbanded fiber cartilage (hyaline and elastic) chondroblast

III fibril, smallbanded fiber

internal organs(e.g., reticular fibers in lymph nodes,

spleen, liver, blood vessels, skin)

fibroblast, reticular cell,smooth muscle cell,

hepatocyte

IV network,sheetlike

basal lamina(lamina densa)

epithelial cell, musclecell, Schawnn cell

V fibril, thin fibril same as type I (polymerizes withtype I fibril to regulate properties)

fibroblast

VII network beneath epithelia (anchoring fibrils) epidermal cells

IX fibril-associated cartilage(lateral association with type II)

chondroblast

X network forming bone(hypertrophic zone of growth plate)

chondrocytes

XI fibril, thin fibril same as type II (polymerizes with type

II fibril to regulate size)

chondroblastEndostatin c-terminal cleavage product of collagens XV and XVIII

INTERACTION OF COLLAGENS


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INTERACTION OF COLLAGENS

III, IV AND VII

Type IV collagen forms a meshwork of procollagen for support and

filtration in the basal lamina.

Type VII collagen anchors the basal lamina to the underlying type I

and III collagens of lamina reticularis of the basement membrane.

IV

IV VII

III


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Network of fibers that allows

passage of cells and fluid

Reticular cells - synthesize

reticular fibers in lymphatic

tissue; cell body and processescompletely surround reticular

fibers

Fibroblasts in CT also make

reticular fibers that support

epithelia, adipocytes, small

blood vessels, nerves, and

muscle cellsLymph node (silver stain)

RETICULAR CONNECTIVE TISSUE

CO AG S AS S


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COLLAGEN DISEASESInherited diseases where the primary genetic defect affects collagen

biosynthesis, post translational modification or extracellular assembly

directly.

Ehlers-Danlos syndrome (s) mutations in collagen I or III or

deficiency in lysyl hydroxylase or procollagen peptidase

abnormal cross-linking of tropocollagen hyperextensible skin

and joints and impaired wound healing

Osteogenesis imperfecta defective biosynthesis of collagen type I.

4 major types, characterized by brittle bones, loose joints and

imperfect dentin formation (dentinogenesis imperfecta)

Scurvy not genetic, dietary deficiency of vitamin C required for

hydroxylation of lysines and prolines. -chains do not form stablehelices and are degraded, weakening CT. Loose teeth, impaired

bone formation and wound healing

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