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Lecturer: Meir M. Barak
Email: [email protected]: Dalton 320Phone: 6433
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BIOL307: Human Anatomy
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Bone tissue lecture outline Bone (organ) definition, function & classification Bone (material) definition & structure Bone cells
Osteoblasts Bone lining cells Osteocytes Osteoclasts
Bone Formation Intramembranous ossification
Endochondral ossification Growth plate Blood supply Modeling and remodeling
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Bone (organ) definition
Bones are rigid organs which buildthe endoskeleton of vertebrates
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Bone (organ) functions
1. Mechanical support & frame, weight bearing &muscle attachment sites (movement)
2. Protection of vital structures3. Hematopoiesis
4. Mineral Homeostasis: mostly calcium & phosphate(More then 99% of calcium is deposited in bones)
[not all bones serves all of those functions]
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Bone (organ) classification
Long bones(tubular)
Flat bones
Short bones
Irregular bones
limbs
parts of the skull,clavicle
Sesamoids*,
carpus/tarsus
Vertebrae, pelvis
*Sesamoid bones are bonesembedded in tendons
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Bone (material) definition
A dense, semi-rigid, porous, calcifiedconnective tissue forming the major
portion of the skeleton of mostvertebrates. It consists of a denseorganic matrix and an inorganic,
mineral component
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Bone material
Elementary components (% by weight): Organic (~24%)
collagen type-I (90%) Noncollagenous proteins (10%)
Mineral - hydroxyapatite [Ca5(PO4)3(OH)] (~70%) Water (~6%)
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Bone mineralize with age
greenstickfracture
comminutedfracture
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Bone is a composite material
Reinforced concreteConcrete compressive strengthReinforcing iron rods tensile and bending strength
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Bone is a composite materialhttp://www.engr.iupui.edu/bme/
bbml/index.shtml
BoneMineral compressive strengthCollagen tensile and bending strength
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Bone is a hierarchical material
http://www.engr.iupui.edu/bme/bbml/index.shtml
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Bone is a hierarchical material
http://www.engr.iupui.edu/bme/bbml/index.shtml
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Bones hierarchical structure
Weiner & Wagner1998
Level 1: Major components
Level 2: Mineralized collagen fibrilLevel 3: Fibril arrayLevel 4: Fibril array patternLevel 5: Osteons / hemi-osteons
Level 6: Cortical / trabecular boneLevel 7: Whole bone(not all levels are manifested in every bone)
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Level 1: Major components
Barth, 2010http://www.azonano.com/article.aspx?ArticleID=2267
hydroxyapatite
~50x25x1.5 nm
Bone tissue structure, function & development
Collagen type-I
Polypeptide chain
Mineralizedcollagen fibril
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The mineralized collagen fibril is bonesbasic building block
Hansma Lab, UCSB Weiner and Traub (1986)
Bone tissue structure, function & development
Level 2: Mineralized collagen fibril
Mineralized collagen fibril
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Level 3: Fibril array
Weiner & Wagner 1998
Bundles of collagen fibrils aligned along theirlong axis
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Weiner & Wagner1998
Dentin
Bone tissue structure, function & development
Thickness of a lamellae
Level 4: Fibril array pattern
Woven
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Level 5: OsteonsWeiner & Wagner
1998
Concentric onion-like lamellarstructure (100-200m).
Run almost parallel to the long axis of the bone.May be laid de-novo or replace older bone(remodeling). In the later case, they are also calledHaversian systems.
Dog bone osteonsLight microscopy
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Woven boneIt is laid down very rapidly and randomly
(no lamellae) and replaced (remodeling) bylamellar bone (Haversian systems).
Common in young animals(mainly large mammals),in fracture calluses and in
some bone tumors (e.g.Osteosarcoma)
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Level 6: Cortical / trabecular boneWeiner & Wagner 1998
Compact / cortical:main component of long bones &the outer shell/surface of short bones; ~5% porosity.
Trabecular :lies within the cortical shell at theextremities of long bones and within short bones; 50-90% porosity. (Trabecular = Cancellous = Spongy)
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Level 6: Cortical / trabecular bone
Bone tissue structure, function & developmentMcGraw Hill (c) Saladin 6
th
ed.
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Level 7: Whole bone
Articular cartilage (hyaline)at the bone ends
Bone tissue structure, function & development
Epiphysisends of long bones, mostlymade up of spongy bone + redmarrow
McGraw Hill (c) Saladin 6th
ed.
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Level 7: Whole bone
Metaphysis: where new bone forms
Bone tissue structure, function & development
Physisgrowth plate (hyaline cartilage)
Diaphysisshaft, compact boneand medullary cavity
McGraw Hill (c) Saladin 6th
ed.
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Level 7: Whole bone - MembranesExternal = periosteum
Outer: connective tissue; Inner: osteogenic layerLots of nerve fibers, blood/lymphatic vessels
Internal = endosteumInner surface of cortical bone and central canals
Contains osteoclasts & osteoblasts
Bone tissue structure, function & development
Superficial?Deep?
McGraw Hill (c) Saladin 6th
ed.
Site of endosteum
Periosteum
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Bone cells
Bone cells originates from 2 cell lines:1. Mesenchymal stem-cell line
Osteoblasts (active deposit)
Bone lining cells (quiescence)
Osteocytes (mature osteoblasts)
2. Hematopoietic stem cell line Osteoclasts (active resorption)
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Deposit osteoid which will later mineralized
Active osteoblast may follow 1 of 3 courses1. Disappear from site of bone formation
2. Remain on the bone surface but turn flat and stopits activity, turning intobone lining cells3. Surround themselves with matrix and become
osteocytes
Osteoblasts - bone builders
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Bone lining cells
Resting osteoblasts Cytoplasmic processes of extend through the
matrix to contact with osteocytes Remove the osteoid seam from the mineralized
matrix and enable Osteoclastto resorb bone
Seeman E, Delmas PD 2006
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Osteocytes The majority of bone cells (>90%) Mature osteoblast imprisoned in lacunae Are connected to each other and to osteoblast and
bone lining cells through cell processes runningin canaliculi (lacunocanalicular system)
Serve as thebone nervous system
Buckwalter 1995
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Osteoclasts bone resorbing cells
Precursor cells found in bone marrow orblood stream Can resorb bone from surfaces (Howship's
lacuna) or from within the cortical bone
(Cutting cone)
Howship lacuna
Cutting cone
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Osteoblasts & Osteoclasts
Bone tissue structure, function & development
http://www.youtube.com/watch?v=78RBpWSOl08
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Bone formation
The formation of bone is calledossificationorosteogenesis
There are 2 pathways for bone to be created:1. Intramembranousossification
mesenchymebone2. Endochondral ossification
mesenchymecartilage anlagebone
The key difference between these 2 processes
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Intramembranous ossification Produces the flat bones of the skull and most of
the clavicle
http://goo.gl/1y0hV
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Intramembranous ossification It is also an essential process during the natural
healing of bone fractures
Callus a step towardfracture healing
Doblare 2004
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Intramembranous ossification
Embryonic mesenchyme(primitive connectivetissue)
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Intramembranous ossification
Embryonic mesenchyme(primitive connectivetissue) condenses and angiogenesisstarts.
Mesenchymal cells grow in size anddifferentiate into osteogeniccells.
McGraw Hill (c) Saladin 6thed.
Mesenchymal cell
Sheet of condensing
mesenchyme
Blood
capillary
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Intramembranous ossification Osteogenic cells differentiate into
osteoblastswhich start to deposit osteoid(remember, mostly collagen type-1)
The osteoid starts to mineralize
Fibrousperiosteum
Osteoid tissue
Calcified bone
Osteoblasts
Osteocyte
McGraw Hill (c) Saladin 6thed.
Trapped osteoblasttransform into
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Intramembranous ossification A network of trabecular-like structure
starts to appear (bone spicules).
Fibrousperiosteum
Calcified boneTrabecula
McGraw Hill (c) Saladin 6thed.
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Intramembranous ossification
Moreand more trabeculae are forming andmineralizing
McGraw Hill (c)Saladin 6thed.
MarrowcavityOsteocytes
Trabeculae
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Intramembranous ossification Trabeculae at the surface continue to
mineralize until the spaces between themare filledcreating the cortex
The typical sandwich-like structure of flat
bone is created
McGraw Hill (c) Saladin 6thed.
Compact bone
Spongy bone
Osteoblasts
Fibrous periosteum
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Intramembranous ossification
Periosteum:Fibrous layer
Osteogeniclayer
Osteoid tissue
Osseous tissue
(bone)
Osteoblasts
Osteocytes
McGraw Hill (c) Saladin 6thed.
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Endochondral ossification
A process where bone develops
from a preexisting model made ofhyaline cartilage
In humans
begins in the embryo at ~6w andends at around 18-20y
http://goo.gl/1y0hV
Cartilage blue
Bone - red
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Endochondral ossification Early embryo stage mesenchyme develops into
hyaline cartilage modelsurrounded byperichondrium
McGraw Hill (c) Saladin 6thed.
Perichondrium
Hyaline cartilage
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E d h d l f
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Endochondral ossification The cartilage model will elongateby extracellular
matrix secretion and chondrocyte cell division(interstitial growth)
The cartilage model will
thickenby addition ofextracellular matrix to thesurface and newchondroblasts createdfrom the perichondrium(appositional growth)
McGraw Hill (c) Saladin 6thed.
Hyalinecartilage
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E d h d l f
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Endochondral ossification Perichondriumdevelops into periosteumand
starts to produce osteoblasts
McGraw Hill (c) Saladin 6thed.
Periosteum
Bone tissue structure, function & development
E d h d l ifi i
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Endochondral ossification Osteoblasts deposit a thinbony collararound
the diaphysis (reinforcement)
McGraw Hill (c) Saladin 6thed.
Periosteum
Bonycollar
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E d h d l ifi i
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Endochondral ossification
The matrix between the cellsreduces into thin walls whichcalcify, blocking nutrients fromreaching the chondrocytes
The chondrocytes secrete VascularEndothelial Growth Factor (vEGF)
The chondrocytes die (apoptosis)and the calcified walls are destroyed
McGraw Hill (c) Saladin 6thed.
Bone tissue structure, function & development
E d h d l ifi i
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Primary
marrowcavity
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Endochondral ossification
Blood vessels invade the primaryossification center and the spaceis filled with blood and stemcells, creating the primary
marrow cavity Stem cells differentiate to
osteoblasts and osteoclasts
McGraw Hill (c) Saladin 6thed.
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E d h d l ifi i
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Primary
marrowcavity
Secondaryossification
center
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Endochondral ossification Chondrocyte in the epiphysis start also to enlarge,
creating the secondary ossification center
McGraw Hill (c) Saladin 6thed.
Epiphysis
Diaphysis
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E d h d l ifi ti
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Endochondral ossification
Chondrocytes in the diaphysiscontinue to die toward the endsof the bone, as the bony collarthickens and elongate.
Osteoclasts follow and increasethe marrow cavity
The region of transition from
cartilage to bone is formed(metaphysis)
McGraw Hill (c) Saladin 6thed.
D
iaphysis
Metaphysis
Bloodvessel
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Endochondral ossification
Chondrocyte in the epiphysis
start to die forming thesecondary marrow cavity.
At this stage - the epiphysisisstill cartilaginous.
That is the state at birth
McGraw Hill (c) Saladin 6thed.
Epiphysis
Metaphysis
Secondarymarrowcavity
Secondaryossificationcenter
Bone tissue structure, function & development
E d h d l ifi ti
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http://goo.gl/1y0hV
Endochondral ossification
Bone tissue structure, function & development
E d h d l ifi ti
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Endochondral ossification
During infancy and childhood theepiphyses are filled with trabecular
bone and the cartilage is limitedjust to the joint surface and thegrowth plate (physis).
Cartilage(outer covering)
Metaphysis
Epiphysealplate
McGraw Hill (c) Saladin 6thed.
Bone tissue structure, function & development
E d h d l ifi ti
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Endochondral ossification
Around 18-20y (human), thegrowth plate is consumed(closed) and is replaced by theepiphyseal line
The primary and secondarymarrow cavities are united
The bone can no longer grow
in length
McGraw Hill (c) Saladin 6thed.
Marrowcavity
Periosteum
Epiphysealline
Spongy
bone
Articular cartilage
Compact
bone (cortex)
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G th l t i t titi l th
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Growth plate - interstitial growth
Epiphyseal end
Diaphysis
Reserve cartilage: resting chondrocytes
(1) Cell proliferation:chondrocytedivide (columns), collagen fibersforming longitudinal septa
(2) Cell hypertrophy:chondrocytes stopto divide & start to increase in size
(3) Calcification:septa calcified
(4) bone deposition:chondrocytes die
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G th l t a eak oi t
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Growth plate a weak point
A fracture that involves the growth plate
a very common injury in growing children is(around 15% of all fractures)
Also known as aSalterHarris fracture
Wikipedia
bone
boneCartilage
Proximal tibia, rabbit
Jaramillo et al. 2000
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Bo e blood u ly
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Bone blood supplyNutrient artery: enters the diaphysis through the nutrientforamen
Periosteal arteries: enter the cortex via Volkmanns canals
Epiphyseal arteries & metaphyseal arteries: anastomose witheach other only after closer of growth plate
http://goo.gl/1y0hV
Bone tissue structure, function & development
Metaphysealartery
Epiphysealartery
Bo e blood supply
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http://goo.gl/8yblR http://goo.gl/KP2Mz
Haversian canals run parallel to the long axis of
the bone Volkmann's canals run perpendicular to the long
axis of the bone. They interconnect Haversiancanals with each other and with the periosteum
Bone blood supply
Bone tissue structure, function & development
Volkmann'scanals
Bone modeling and remodeling
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Bone modeling and remodeling
Contrary to what you might think bone is not astatic tissue
On the contrary, it constantly changes and adjust in
response to stimulus
Bone tissue structure, function & development
McGraw Hill (c) Saladin 6thed.
Bone modeling
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Bone modeling
Initiated by increased/decreases load or change
in direction of loading
Osteoblastsand/or osteoclastsdepositand or resorb bone
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Bone remodeling
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Bone remodeling In addition to bone growth, bone is being
remodeled throughout life (initiated by damage tothe bone)
Remodeling happens both in trabecular and
cortical bone The end product of cortical bone remodeling is
secondary osteons (Haversian systems)
Bone tissue structure, function & development
Cutting cone
Haversian system ( d t )
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Haversian system (secondary osteons)
Robling & Stout 1999
Schaffler et al. 1987
Cement line
Replace older bone (remodeling)
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Modeling vs Remodeling
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Modeling vs. Remodeling
Modeling Remodeling
Initiated byincreased/decreases load
Initiated by damage to thebone
May involve resorption and/or
deposition
resorption and deposition are
coupled
Resorption and depositionmay occur at different sites
Resorption and depositionalways happen at the same site
Involves relatively large mountof bone Involves very small amountsof bone
Bone tissue structure, function & development
When remodeling goes astray
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When remodeling goes astrayImbalance in function will lead to pathologies:
OsteoporosisExcessive bone resorption by osteoclasts or inadequateformation of new bone by osteoblasts
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Overview questions
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Overview questions1. What are the 3 elementary components of bone?2. Explain 2 bone functions3. Explain why bone is a composite material4. What is the main difference between cortical & trabecular
bone?5. Name 2 bone cell types and explain briefly their role
6. What are lacunae and canaliculi?7. What is the key difference between intramembranous and
endchondral ossification?8. Which type of cartilage is replaced by bone in endchondral
ossification?9. What is the difference between interstitial and appositionalgrowths?
10. Explain in short how the growth plate elongate bones11 Give 2 differences between modeling and remodeling