L04 Bone Tissue

8/11/2019 L04 Bone Tissue

1/66

Lecturer: Meir M. Barak

Email: [email protected]: Dalton 320Phone: 6433

5/30/2014 1

BIOL307: Human Anatomy
mailto:[email protected]:[email protected]


2/66

5/30/2014 2

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

Bone tissue structure, function & development


3/66

5/30/2014 3

Bone (organ) definition

Bones are rigid organs which buildthe endoskeleton of vertebrates



4/66

5/30/2014 4

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]



5/66

5/30/2014 5

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



6/66

5/30/2014 6

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



7/665/30/2014 7

Bone material

Elementary components (% by weight): Organic (~24%)

collagen type-I (90%) Noncollagenous proteins (10%)

Mineral - hydroxyapatite [Ca5(PO4)3(OH)] (~70%) Water (~6%)



8/665/30/2014 8

Bone mineralize with age

greenstickfracture

comminutedfracture



9/665/30/2014 9

Bone is a composite material

Reinforced concreteConcrete compressive strengthReinforcing iron rods tensile and bending strength



10/665/30/2014 10

Bone is a composite materialhttp://www.engr.iupui.edu/bme/

bbml/index.shtml

BoneMineral compressive strengthCollagen tensile and bending strength



11/665/30/2014 11

Bone is a hierarchical material

http://www.engr.iupui.edu/bme/bbml/index.shtml



12/665/30/2014 12

Bone is a hierarchical material

http://www.engr.iupui.edu/bme/bbml/index.shtml



13/66

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)

5/30/2014 13Bone tissue structure, function & development


14/665/30/2014 14

Level 1: Major components

Barth, 2010http://www.azonano.com/article.aspx?ArticleID=2267

hydroxyapatite

~50x25x1.5 nm


Collagen type-I

Polypeptide chain

Mineralizedcollagen fibril


15/665/30/2014 15

The mineralized collagen fibril is bonesbasic building block

Hansma Lab, UCSB Weiner and Traub (1986)


Level 2: Mineralized collagen fibril

Mineralized collagen fibril


16/665/30/2014 16

Level 3: Fibril array

Weiner & Wagner 1998

Bundles of collagen fibrils aligned along theirlong axis



17/665/30/2014 17

Weiner & Wagner1998

Dentin


Thickness of a lamellae

Level 4: Fibril array pattern

Woven


18/665/30/2014 18

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



19/66

5/30/2014 19

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)



20/66

5/30/2014 20

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)



21/66

5/30/2014 21

Level 6: Cortical / trabecular bone

Bone tissue structure, function & developmentMcGraw Hill (c) Saladin 6

th

ed.


22/66

5/30/2014 22

Level 7: Whole bone

Articular cartilage (hyaline)at the bone ends


Epiphysisends of long bones, mostlymade up of spongy bone + redmarrow

McGraw Hill (c) Saladin 6th

ed.


23/66

5/30/2014 23

Level 7: Whole bone

Metaphysis: where new bone forms


Physisgrowth plate (hyaline cartilage)

Diaphysisshaft, compact boneand medullary cavity


ed.


24/66

5/30/2014 24

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


Superficial?Deep?


ed.

Site of endosteum

Periosteum


25/66

5/30/2014 25

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)



26/66

5/30/2014 26

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



27/66

5/30/2014 27

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



28/66

5/30/2014 28

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



29/66

5/30/2014 29

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



30/66

5/30/2014 30

Osteoblasts & Osteoclasts


http://www.youtube.com/watch?v=78RBpWSOl08
http://www.youtube.com/watch?v=78RBpWSOl08http://www.youtube.com/watch?v=78RBpWSOl08


31/66

5/30/2014 31

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



32/66

5/30/2014 32

Intramembranous ossification Produces the flat bones of the skull and most of

the clavicle

http://goo.gl/1y0hV



33/66

5/30/2014 33

Intramembranous ossification It is also an essential process during the natural

healing of bone fractures

Callus a step towardfracture healing

Doblare 2004



34/66

5/30/2014 34

Intramembranous ossification

Embryonic mesenchyme(primitive connectivetissue)



35/66

5/30/2014 35


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



36/66

5/30/2014 36

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


Trapped osteoblasttransform into



37/66

5/30/2014 37

Intramembranous ossification A network of trabecular-like structure

starts to appear (bone spicules).

Fibrousperiosteum

Calcified boneTrabecula




38/66

5/30/2014 38


Moreand more trabeculae are forming andmineralizing

McGraw Hill (c)Saladin 6thed.

MarrowcavityOsteocytes

Trabeculae



39/66

5/30/2014 39

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


Compact bone

Spongy bone

Osteoblasts

Fibrous periosteum



40/66

5/30/2014 40


Periosteum:Fibrous layer

Osteogeniclayer

Osteoid tissue

Osseous tissue

(bone)

Osteoblasts

Osteocytes




41/66

5/30/2014 41

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



42/66

5/30/2014 42

Endochondral ossification Early embryo stage mesenchyme develops into

hyaline cartilage modelsurrounded byperichondrium


Perichondrium

Hyaline cartilage


E d h d l f


43/66

5/30/2014 43

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)


Hyalinecartilage


E d h d l f


44/66

5/30/2014 44

Endochondral ossification Perichondriumdevelops into periosteumand

starts to produce osteoblasts


Periosteum


E d h d l ifi i


45/66

5/30/2014 45

Endochondral ossification Osteoblasts deposit a thinbony collararound

the diaphysis (reinforcement)


Periosteum

Bonycollar



46/66

E d h d l ifi i


47/66

5/30/2014 47


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



E d h d l ifi i


48/66

Primary

marrowcavity

5/30/2014 48


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



E d h d l ifi i


49/66

Primary

marrowcavity

Secondaryossification

center

5/30/2014 49

Endochondral ossification Chondrocyte in the epiphysis start also to enlarge,

creating the secondary ossification center


Epiphysis

Diaphysis


E d h d l ifi ti


50/66

5/30/2014 50


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)


D

iaphysis

Metaphysis

Bloodvessel


E d h d l ifi ti


51/66

5/30/2014 51


Chondrocyte in the epiphysis

start to die forming thesecondary marrow cavity.

At this stage - the epiphysisisstill cartilaginous.

That is the state at birth


Epiphysis

Metaphysis

Secondarymarrowcavity

Secondaryossificationcenter


E d h d l ifi ti


52/66

5/30/2014 52

http://goo.gl/1y0hV



E d h d l ifi ti


53/66

5/30/2014 53


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



E d h d l ifi ti


54/66

5/30/2014 54


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


Marrowcavity

Periosteum

Epiphysealline

Spongy

bone

Articular cartilage

Compact

bone (cortex)



55/66

G th l t i t titi l th


56/66

5/30/2014 56

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


G th l t a eak oi t


57/66

5/30/2014 57

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


Bo e blood u ly


58/66

5/30/2014 58

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


Metaphysealartery

Epiphysealartery

Bo e blood supply


59/66

5/30/2014 59

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


Volkmann'scanals

Bone modeling and remodeling


60/66

5/30/2014 60

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 modeling


61/66

5/30/2014 61

Bone modeling

Initiated by increased/decreases load or change

in direction of loading

Osteoblastsand/or osteoclastsdepositand or resorb bone


Bone remodeling


62/66

5/30/2014 62

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)


Cutting cone

Haversian system ( d t )


63/66

5/30/2014 63

Haversian system (secondary osteons)

Robling & Stout 1999

Schaffler et al. 1987

Cement line

Replace older bone (remodeling)


Modeling vs Remodeling


64/66

5/30/2014 64

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


When remodeling goes astray


65/66

5/30/2014 65

When remodeling goes astrayImbalance in function will lead to pathologies:

OsteoporosisExcessive bone resorption by osteoclasts or inadequateformation of new bone by osteoblasts


Overview questions


66/66

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

Documents

L04 Bone Tissue