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Connective Tissue ProperConnective Tissue ProperConnective Tissue ProperConnective Tissue Proper
Won Taek Lee, M.D., Ph.D.Won Taek Lee, M.D., Ph.D.Won Taek Lee, M.D., Ph.D.Won Taek Lee, M.D., Ph.D.
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Connective TissueConnective TissueConnective TissueConnective Tissue
CharacteristicsCharacteristics
1. abundant 1. abundant intercellular substanceintercellular substance
2. diversity of cellular components2. diversity of cellular components
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Connective TissueConnective TissueConnective TissueConnective Tissue
ClassificationClassification
Connective Tissue ProperConnective Tissue Proper
Adipose TissueAdipose Tissue
Specialized Connective TissueSpecialized Connective Tissue
Bone and CartilageBone and Cartilage
Blood and Hemopoietic TissueBlood and Hemopoietic Tissue
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Connective Tissue ProperConnective Tissue ProperConnective Tissue ProperConnective Tissue Proper
Cellular ComponentsCellular Components
Fixed cellsFixed cells Wandering cellsWandering cells
Intercellular Substance (Matrix)Intercellular Substance (Matrix) FibersFibers Ground substanceGround substance
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Cellular ComponentsCellular ComponentsCellular ComponentsCellular Components
1. Fibroblast - Fibrocyte1. Fibroblast - Fibrocyte 2. Macrophage system2. Macrophage system3. Mast cell3. Mast cell4. Plasma cell4. Plasma cell5. Adipose cell5. Adipose cell6. Mesenchymal cell6. Mesenchymal cell6. Others: 6. Others: leukocytes, smooth muscle cell, pericytesleukocytes, smooth muscle cell, pericytes
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Fibroblast - FibrocyteFibroblast - FibrocyteFibroblast - FibrocyteFibroblast - Fibrocyte
blastic activity - intercellular substanceblastic activity - intercellular substance
---- protein synthesizing cells in active state---- protein synthesizing cells in active state
limited activity in resting stage (fibrocyte)limited activity in resting stage (fibrocyte)
-blast, -cyte change-blast, -cyte change
osteoblast - osteocyteosteoblast - osteocyte
chondroblast - chondrocytechondroblast - chondrocyte
cementoblastt - cementocytecementoblastt - cementocyte
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Fibroblast - FibrocyteFibroblast - Fibrocyte
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Fibroblast - FibrocyteFibroblast - Fibrocyte
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FibroblastFibroblast
FibrocyteFibrocyte
Function:Function:
Fibers (collaen, elastic)Fibers (collaen, elastic)
and ground substanceand ground substance
(proteoglycan)(proteoglycan)
production.production.
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MacrophageMacrophage System SystemMacrophageMacrophage System System
high high phagocyticphagocytic activity activity ---- secondary---- secondary lysosomelysosome precursor cell ---- blood precursor cell ---- blood monocytemonocyte
Mononuclear phagocytic system (MPS)Mononuclear phagocytic system (MPS) CTP ----------CTP ---------- histiocytehistiocyte liver ----------liver ---------- Kupffer cellKupffer cell lung ----------lung ---------- dust cell (alveolar macrophage)dust cell (alveolar macrophage) bone ---------bone --------- osteoclastosteoclast CNS ---------CNS --------- microgliamicroglia Placenta -----Placenta ----- Hofbauer cellHofbauer cell
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MacrophageMacrophage
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Mast CellMast CellMast CellMast Cell
Large cell, 20-30 Large cell, 20-30 m in diameterm in diameter
with small nucleus,with small nucleus, filled with abundantfilled with abundant secretory granulessecretory granules prominent Golgiprominent Golgi
Secretory Secretory (metachromatic)(metachromatic) granule granule
0.3-0.5 0.3-0.5 m in diameterm in diameter storage of chemical mediators of storage of chemical mediators of immediate type immune responseimmediate type immune response metachromasiametachromasia due to due to heparinheparin and other and other glycosaminoglycansglycosaminoglycans
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Mast CellMast Cell
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Mast CellMast Cell
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Mast Mast
CellCell
degranulationdegranulation
IgEIgE
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Plasma CellPlasma CellPlasma CellPlasma Cell
AntibodyAntibody (Ab)(Ab) producing cellproducing cell Protein synthesizing cellProtein synthesizing cell cart wheel (clock face)cart wheel (clock face) appearanceappearance ------ chromatin pattern------ chromatin pattern cytoplasmic cytoplasmic basophiliabasophilia ------ abundant rER------ abundant rER perinuclear halo perinuclear halo ----- Golgi complex----- Golgi complex Chronic inflammatory cellChronic inflammatory cell humoralhumoral immune response immune response Precursor cellPrecursor cell ----- ----- B lymphocyteB lymphocyte
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Plasma CellPlasma Cell
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Plasma CellPlasma Cell
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Adipose (Fat) CellAdipose (Fat) CellAdipose (Fat) CellAdipose (Fat) Cell
WhiteWhite (unilocular)(unilocular) adipose cell adipose cell 20-100 20-100 m in diameterm in diameter single central single central lipid dropletlipid droplet peripheral nucleusperipheral nucleus signet ring cellsignet ring cell
BrownBrown (multilocular)(multilocular) adipose cell adipose cell 15-25 15-25 m in diameterm in diameter abundant abundant mitochondriamitochondria and and lipid dropletlipid droplet heat generationheat generation
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White Adipose (Fat) CellWhite Adipose (Fat) Cell
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White Adipose White Adipose
(Fat) Cell(Fat) Cell
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Brown Adipose Brown Adipose
(Fat) Cell(Fat) Cell
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NorepinephrineNorepinephrine
Adenyl cyclase activationAdenyl cyclase activation
Lipase activationLipase activation
Fatty acids releaseFatty acids release
Oxidation in mitochondriaOxidation in mitochondria
Heat generationHeat generation
Brown Adipose Brown Adipose
Cell FunctionCell Function
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Mesenchymal CellMesenchymal CellMesenchymal CellMesenchymal Cell
small stellate cell small stellate cell 7-10 mm in diameter7-10 mm in diameter not easily distinguished from fibrocytenot easily distinguished from fibrocyte
Pluripotential (totipotential) stem cellPluripotential (totipotential) stem cell precursor of connective tissue cellprecursor of connective tissue cell of embryonic of embryonic mesenchymemesenchyme small population of cells of mesenchymesmall population of cells of mesenchyme persist into postnatal life and persist into postnatal life and differntiate to form other CT cellsdifferntiate to form other CT cells
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Mesenchymal Mesenchymal
CellCell
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Connective Tissue FiberConnective Tissue FiberConnective Tissue FiberConnective Tissue Fiber
1. Collagen fiber ----1. Collagen fiber ---- type I collagentype I collagen
2. Reticular fiber ----2. Reticular fiber ---- type III collagentype III collagen
3. Elastic fiber -------3. Elastic fiber ------- elastin, fibrillinelastin, fibrillin
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Collagen FiberCollagen FiberCollagen FiberCollagen Fiber
• AcidophilicAcidophilic thick, birefringent thick, birefringent• Very resistant to tractionVery resistant to traction
- extensibility ---- 5%- extensibility ---- 5%
- very high - very high tensile strengthtensile strength
• Most abundantMost abundant proteins of the body proteins of the body - 30-35% of dry body weight- 30-35% of dry body weight - 20% of total body proteins- 20% of total body proteins
• High in glycine, alanine, proline,High in glycine, alanine, proline, hydroxyproline, hydroxylysinehydroxyproline, hydroxylysine poor in sulfur, no tryptophanpoor in sulfur, no tryptophan
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Collagen FiberCollagen Fiber
dermisdermis
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Collagen FiberCollagen Fiber
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• Collagen fiber bundleCollagen fiber bundle
Collagen Fiber --------------------------- Collagen Fiber --------------------------- 5-15 5-15 mm
Collagen Fibril ------------------------ Collagen Fibril ------------------------ 0.3-2 0.3-2 mm
Collagen Microfibril -------------- Collagen Microfibril -------------- 5-20 nm5-20 nm
Collagen Protofibril ------------ Collagen Protofibril ------------ 4.5 nm4.5 nm
Tropocollagen Molecules - Tropocollagen Molecules - 1.5 nm1.5 nm
• Periodicity of Collagen FibrilsPeriodicity of Collagen Fibrils
- longitudinal arrangement of tropocollagen molecules- longitudinal arrangement of tropocollagen molecules
0.6 D (38.4 nm) gap --- lacunar region0.6 D (38.4 nm) gap --- lacunar region
- stepwise arrangement- stepwise arrangement
overapping region --- ~10% of tropocollagen length overapping region --- ~10% of tropocollagen length
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Collagen FibrilsCollagen Fibrils
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Collagen SynthesisCollagen Synthesis
Intracellular ProcessIntracellular Process
Nucleus --------Nucleus -------- mRNA transcription mRNA transcription
Ribosome -----Ribosome ----- transcription of preprocollage transcription of preprocollage
nn rER cisterna --rER cisterna -- hydroxylation and glycosylatio hydroxylation and glycosylatio
n, n, formation of procollagen triple helix formation of procollagen triple helix
Golgi ------------Golgi ------------ secretion of procollagen secretion of procollagen
Extracellular ProcessExtracellular Process
Propeptidase convert procollagen toPropeptidase convert procollagen to
tropocollagentropocollagen
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Process of Process of
Collagen SCollagen S
ynthesisynthesis
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Major Collagen TypesMajor Collagen Types
Type Procollagen morphology Tissue Distribution Disease
I [1(I)]2 2(I)] fiber (collagen)
bone, skin, tendon, ligament, dentin, cementum
osteogenesis imperfecta
II [1(II)]3 fiber cartilage chondrodysplasia
III [1(III)]3fiber (reticula
r)
skin, arteries, reticular tissues and organs, liver
Ehlers-Danlos syndrome type IV
IV [1(IV)]2 2(IV)] sheet basement membrane Alport's syndrome
V [1(V)]2 2(V)] fiberfetal tissues, placenta, interstitial tissues
VII [1(VII)]3anchoring fibr
iljunction of epidermis and dermis
epidermolysis bullosa
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Collagen Types Collagen Types
Type I collagen Type I collagen Type IV collagenType IV collagen
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Collagen defectsCollagen defects ScurvyScurvy – deficiency of Vitamine C, – deficiency of Vitamine C,
cofactor for proline hydroxylasecofactor for proline hydroxylase Ehlers-DanlosEhlers-Danlos syndrome syndrome typetype VIVI – – faulty lysyl hydroxylation, kyposcoliosis faulty lysyl hydroxylation, kyposcoliosis
Ehlers-DanlosEhlers-Danlos syndrome syndrome typetype IVIV – – defects in type III collagen, vascular abnormalities defects in type III collagen, vascular abnormalities Ehlers-DanlosEhlers-Danlos syndrome syndrome typetype IVIV – – defects in procollagen peptidase, articular abnormalities defects in procollagen peptidase, articular abnormalities Osteogenesis imperfectaOsteogenesis imperfecta – type I collagen gene mutation – type I collagen gene mutation
ChondrodysplasiaChondrodysplasia – type II collagen gene mutation – type II collagen gene mutation
Alport’s syndromeAlport’s syndrome – type IV collagen (BM) anomaly – type IV collagen (BM) anomaly
Collagen excess: Collagen excess: Fibrosis, Kelloid, CirrhosisFibrosis, Kelloid, Cirrhosis
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ScurvyScurvyVitamine C (cofactor for proline hydrVitamine C (cofactor for proline hydr
oxylase) Deficiencyoxylase) Deficiency
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Scurvy – Historical diseaseScurvy – Historical diseaseJames LindJames Lind(1716-1794)(1716-1794)
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Ehlers-Danlos syndromeEhlers-Danlos syndrome
Defects in collagen synthesis – High elasticityDefects in collagen synthesis – High elasticity
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Osteogenesis ImperfectaOsteogenesis Imperfecta
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Alport’sAlport’s
syndromesyndrome
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Reticular FiberReticular FiberReticular FiberReticular Fiber
• Argyrophilic, PAS-positive, thin (0.5-2 m) fiberArgyrophilic, PAS-positive, thin (0.5-2 m) fiber
Structural maintenance in expansile organ.Structural maintenance in expansile organ.
• Type III CollagenType III Collagen
6-12% hexoses (1% in collagen type I)6-12% hexoses (1% in collagen type I) Collagen microfibrils + Proteogycan interfibrillar bridgeCollagen microfibrils + Proteogycan interfibrillar bridge
• Immature FiberImmature Fiber
Abundant in embryonic tissues and wound healingAbundant in embryonic tissues and wound healing
• Reticular Tissue, Glands, Large Vessels, Intestinal WallReticular Tissue, Glands, Large Vessels, Intestinal Wall
• Ehlers-DanlosEhlers-Danlos TypeType IVIV (Faulty transcription/translation of (Faulty transcription/translation of Type III Collagen)Type III Collagen)
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Reticular FiberReticular Fiber
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Elastic FiberElastic FiberElastic FiberElastic Fiber
• 0.1-10 0.1-10 m thick fiberm thick fiber
• High Elasticity (rubber-like consistency)High Elasticity (rubber-like consistency)
• Special stain: resorcin fuchsin, aldehyde fuchsin, Special stain: resorcin fuchsin, aldehyde fuchsin,
van Gieson (mordant hematoxylin), and orceinvan Gieson (mordant hematoxylin), and orcein
• Distribution: Elastic Connective TissueDistribution: Elastic Connective Tissue
ligamentum nucha, ligamentum flavaligamentum nucha, ligamentum flava
vocal ligaments, stylohyoid ligementvocal ligaments, stylohyoid ligement
elastic membrane and lamellae of arteryelastic membrane and lamellae of artery
elastic cartilageelastic cartilage
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Elastic FiberElastic FiberElastic FiberElastic Fiber
Elastin, central (Pars Amorpha)Elastin, central (Pars Amorpha)
glycine (half), proline (10%), hydroxyprolineglycine (half), proline (10%), hydroxyproline
desmosine, isodesmosinedesmosine, isodesmosine
Microfibrils, peripheral (Pars Filamentosa)Microfibrils, peripheral (Pars Filamentosa)
11-13 nm in diameter11-13 nm in diameter
Fibrillin: Fibrillin:
no isodesmosine, desmosine, hydroxyprolineno isodesmosine, desmosine, hydroxyproline
half-cystine residue, 5% neutral sugarhalf-cystine residue, 5% neutral sugar
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Oxytalan FiberOxytalan Fiber
microfibrilmicrofibril no elastinno elastin
Elaunin FiberElaunin Fiberelastin depositionelastin deposition
microfibrilmicrofibril
Elastic FiberElastic Fiber
elastin, centralelastin, centralmicrofibril, peripheralmicrofibril, peripheral
Elastic Fiber EvolutionElastic Fiber Evolutionoxytalan
fiber
elauninfiber
elasticfiber
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Elastic FiberElastic Fiber
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Elastic Fiber Elastic Fiber central elastin and peripheral microfibrilscentral elastin and peripheral microfibrils
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Elastic Elastic
Fiber Fiber
stretch stretch andand
relaxationrelaxation
elasticityelasticity
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Defects in Fibrillin – Marfan syndrome Defects in Fibrillin – Marfan syndrome
tall statuetall statue
arachnoidactilyarachnoidactily
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Defects in Fibrillin – Marfan syndrome Defects in Fibrillin – Marfan syndrome
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Marfan syndrome Marfan syndrome
PharaohPharaoh Akhenaten Akhenaten Abraham LincolnAbraham Lincoln
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Ground SubstanceGround SubstanceGround SubstanceGround Substance
ProteoglycanProteoglycan glycosaminoglycan (GAG)glycosaminoglycan (GAG)
made of repeating disaccharide made of repeating disaccharide hexose+hexosaminehexose+hexosamine core poteincore potein test tube brush shapetest tube brush shape sometimes linked tosometimes linked to hyaluronic acidhyaluronic acid
Structural GlycoproteinStructural Glycoprotein fibronectin, laminin, chondronectinfibronectin, laminin, chondronectin
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GAG hexuronic acid hexosamine Distribution
hyaluronic acid
D-glucuronic acid D-glucosaminecartilage, umbilical cord, synovial fluid, vitreous humor
chondroitin-4-sulfate
D-glucuronic acid D-galactosaminecartilage, bone, cornea, skin, notochord, aorta
chondroitin-6-sulfate
D-glucuronic acid D-galactosaminecartilage, umbilical cord, skin, aorta (media)
dermatan sulfate
L-iduronic acid, D-glucuronic acid
D-galactosamineskin, tendon, aorta (adventitia)
heparan sulfate
D-glucuronic acid, D-iduronic acid
D-galactosamineaorta, lung, liver, basal lamina
keratan sulfate (corneal)
D-galactose D-galactosamine cornea
keratan sulfate (skeletal)
D-galactose D-glucosaminecartilage, nucleus pulposus, annulus fibrosus
Glycosaminoglycans (GAG)Glycosaminoglycans (GAG)
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Proteoglycan and Glycosaminoglycans (GAG)Proteoglycan and Glycosaminoglycans (GAG)
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Structural GlycoproteinStructural GlycoproteinStructural GlycoproteinStructural Glycoprotein
Fibronectin LamininFibronectin Laminin
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fibronectinfibronectin
integrinintegrin
interactioninteraction
Extracellular and Extracellular and
intracellularintracellular
integrityintegrity
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Extracellular Matrix and Cellular InteractionExtracellular Matrix and Cellular Interaction
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Connective Tissue ProperConnective Tissue ProperConnective Tissue ProperConnective Tissue Proper
ClassificationClassification
Loose connective tissueLoose connective tissue
Dense connective tissueDense connective tissue
dense regular connective tissuedense regular connective tissue
dense irregular connective tissuedense irregular connective tissue
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Loose Connective TissueLoose Connective Tissue
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Dense Irregular Connective TissueDense Irregular Connective Tissue
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Dense Regular Connective TissueDense Regular Connective Tissue