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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
Recommended