bone formation _Osteogenesis Flowchart.ppt

Osteogenesis- Types

1. Ossification = Osteogenesis
1Physiology of bone formation_V.Mythily,JCE

2. Ossification = Osteogenesis
•Parts of the fetal skeleton form during
the first few weeks after conception
•By the end of the 8
th
week, the skeletal
pattern is formed : cartilage &
connective tissue membranes.
2Physiology of bone formation_V.Mythily,JCE

3. Physiology of Bone formation
•All bone formation is a replacement process. During
development, tissues are replaced by bone during the
ossification process.
•In intramembranous ossification, bone develops directly
from sheets of mesenchymal connective tissue.
•In endochondral ossification, bone develops by replacing
hyaline cartilage. Activity in the epiphyseal plate enables
bones to grow in length (this is interstitial growth).
•Appositional growth allows bones to grow in diameter.
Remodeling occurs as bone is resorbed and replaced by
new bone.
3Physiology of bone formation_V.Mythily,JCE

4. OSSIFICATION-Formation of
bones
•Boneformation,alsocalledossification,process
bywhichnewboneisproduced.
•Ossificationbeginsaboutthethirdmonthoffetal
lifeinhumansandiscompletedby
lateadolescence.
•Theprocesstakestwogeneralforms,one
forcompactbone,whichmakesuproughly80
percentoftheskeleton,andtheother
forcancellousbone,includingpartsoftheskull,
theshoulderblades,andtheendsofthelong
bones.
4Physiology of bone formation_V.Mythily,JCE

5. OSSIFICATION-Formation of
bones
•Bone of the first type begins in the embryonic skeleton with
acartilagemodel, which is gradually replaced by bone.
•Specializedconnectivetissuecellscalledosteoblastssecretea
matrixmaterialcalledosteoid,agelatinoussubstancemadeup
ofcollagen,afibrousprotein,andmucopolysaccharide,an
organicglue.
•Soon after the osteoidis laid down, inorganic salts are
deposited in it to form the hardened material recognized as
mineralized bone.
•The cartilage cells die out and are replaced by
osteoblastsclusteredin ossification centres.
•Bone formation proceeds outward from these centres. This
replacement of cartilage by bone is known asendochondral
ossification.
5Physiology of bone formation_V.Mythily,JCE

6. OSSIFICATION-Formation of
bones
•Most short bones have a single ossification centre
near the middle of the bone; long bones of the
arms and legs typically have three, one at the
centre of the bone and one at each end.
•Ossificationoflongbonesproceedsuntilonlya
thinstripofcartilageremainsateitherend;this
cartilage,calledtheepiphysealplate,persists
untilthebonereachesitsfulladultlengthandis
thenreplacedwithbone.
6Physiology of bone formation_V.Mythily,JCE

7. OSSIFICATION
•Theflatbonesoftheskullarenotpreformedin
cartilagelikecompactbonebutbeginasfibrous
membranesconsistinglargelyofcollagenandblood
vessels.
•Osteoblastssecretetheosteoidintothismembrane
toformaspongelikenetworkofbonyprocesses
calledtrabeculae.
•Thenewboneformationradiatesoutwardfrom
ossificationcentresinthemembrane.Thisprocess
iscalledintermembranousossification.
•Thereareseveralossificationcentresintheskull.
7Physiology of bone formation_V.Mythily,JCE

8. OSSIFICATION & BONE
REMODELLING
•Atbirth,boneformationisincomplete,andsoft
spotscanbefeltbetweenthesecentres.Thelines
wherethenewbonefromadjacentcentres
meetsformcranialsuturesvisibleonthesurface
oftheadultskull.
•Bothendochondralandintermembranous
ossificationproduceimmaturebone,which
undergoesaprocessofboneresorption
anddepositioncalledboneremodelingto
producematurebone.
8Physiology of bone formation_V.Mythily,JCE

9. OSSIFICATION
•Boneremodeling,continuingprocessofsynthesisand
destructionthatgivesboneitsmaturestructureand
maintainsnormalcalciumlevelsinthebody.
•Destruction,orresorption,ofbonebylargecells
calledosteoclastsreleasescalciumintothebloodstreamto
meetthebody’smetabolicneedsandsimultaneously
allowsthebone—whichisinhibitedbyitsinorganic
componentfromgrowingbycelldivisionlikeother
tissues—toaltersizeandshapeasitgrowstoadult
proportions.
•Whiletheosteoclastsresorbboneatvarioussites,other
cellscalledosteoblastsmakenewbonetomaintainthe
skeletalstructure.
•Duringchildhood,boneformationoutpacesdestructionas
growthproceeds.Afterskeletalmaturityisreached,the
twoprocessesmaintainanapproximatebalance.
9Physiology of bone formation_V.Mythily,JCE

10. OSSIFICATION
•Osteoclastsactontheinnersurfacesofbones,inthe
marrowcavityandthespacesofcancellousbone,to
widenthesecavities;theyalsoactontheouter
surfacestoreducebonyprocesses,suchasthe
epiphysealswellingsattheendsofthelongbonesof
thearmandleg.Osteoclastactivitytakesplacebehind
theepiphysealgrowthzonetoreduceformerswellings
tothewidthofthelengtheningshaft.Withinthebone,
osteoclasticdestructionhelpstoconvertimmature
bone(calledwovenbone)intomaturecompact
bone(lamellarbone)byclearinglongtubularspaces
thatwillserveascentresforthedevelopment
ofosteons,thebonystructuresthroughwhichblood
vesselspass.
10Physiology of bone formation_V.Mythily,JCE

11. There are two classifications of
ossification
Intramembranous: Endochondral:
*Replacement of *Replacement of
sheetlike connective hyaline cartilage
tissue with bony tissue with bony tissue
*Primarily in flat bones *Most bones are
of skull & some irregular formed this way
bones
11Physiology of bone formation_V.Mythily,JCE

12. Intra-membranous Ossification
•Duringintra-membranous ossification,
compactandspongybonedevelopsdirectly
from sheets of mesenchymal
(undifferentiated)connectivetissue.
•Theflatbonesoftheface,mostofthecranial
bones,andtheclavicles(collarbones)are
formedviaintramembranousossification.
12Physiology of bone formation_V.Mythily,JCE

13. Intra-membranous Ossification
•Theprocessbeginswhenmesenchymalcells
intheembryonicskeletongathertogetherand
begintodifferentiateintospecializedcells.
•Someofthesecellswilldifferentiateinto
capillaries,whileotherswillbecome
osteogeniccellsandthenosteoblasts.
•Althoughtheywillultimatelybespreadoutby
theformationofbonetissue,earlyosteoblasts
appearinaclustercalledanossification
center.
13Physiology of bone formation_V.Mythily,JCE

14. Intra-membranous Ossification
•Theosteoblastssecreteosteoid,uncalcifiedmatrix
consistingofcollagenprecursorsandotherorganic
proteins,whichcalcifies(hardens)withinafewdays
asmineralsaltsaredepositedonit,thereby
entrappingtheosteoblastswithin.
•Onceentrapped,theosteoblastsbecomeosteocytes
Asosteoblaststransformintoosteocytes,osteogenic
cellsinthesurroundingconnectivetissue
differentiateintonewosteoblastsattheedgesofthe
growingbone.
14Physiology of bone formation_V.Mythily,JCE

15. Intra-membranous Ossification
•Several clusters of osteoid unite around the
capillaries to form a trabecular matrix, while
osteoblasts on the surface of the newly
formed spongy bone become the cellular layer
of the periosteum . The periosteum then
secretes compact bone superficial to the
spongy bone. The spongy bone crowds nearby
blood vessels, which eventually condense into
red bone marrow . The new bone is
constantly also remodeling under the action
of osteoclasts
15Physiology of bone formation_V.Mythily,JCE

16. Intra-membranous Ossification
•Intramembranousossificationbeginsinuteroduring
fetaldevelopmentandcontinuesoninto
adolescence.
•Atbirth,theskullandclaviclesarenotfullyossified
norarethejunctionsbetweentheskullbone
(sutures)closed.
•Thisallowstheskullandshoulderstodeformduring
passagethroughthebirthcanal.Thelastbonesto
ossifyviaintramembranousossificationaretheflat
bonesoftheface,whichreachtheiradultsizeatthe
endoftheadolescentgrowthspurt.
16Physiology of bone formation_V.Mythily,JCE

17. Intra-membranous Ossification
17Physiology of bone formation_V.Mythily,JCE

18. 18Physiology of bone formation_V.Mythily,JCE

19. Intramembranous
Ossification
•At mesoderm-mesenchymal cell condense
& vascularised
•Condensed mesenchymal cell-lay down
collagen fibres
•Condensed mesenchymal cell has stem cell
–differentaiation into osteoblast (bone
forming cells)
•Osteoblast –synthesise osteoid matrix(
Type I collagen+ ground substance (ECF &
Proteoglycan)
19Physiology of bone formation_V.Mythily,JCE

20. Intra-membranous Ossification
•Osteoid matrix –calcified by osteoblast ms
•Osteoblast get trapped into the matrix-
forming Osteocytes
•Osteocytes have cytoplasmic process and act
as ossification centres
•Many ossification centres fuse. Bone matrix
organises into rods and plates.-Trabeculae of
cancellous bone forms around the blood
vessels.
20Physiology of bone formation_V.Mythily,JCE

21. Intra-membranous Ossification
•Between trabeculae –haemopoietic tissue
present.
•Now mesenchymal cells become blood
forming cells (marrow)
•Mesenchyma around bone marrow does not
form bone. It forms periosteum to cover
marrow.
•Then it forms endosteum to cover trabeculae.-
immature woven bone develops
21Physiology of bone formation_V.Mythily,JCE

22. Intra-membranous Ossification
•Modellingofimmaturewovenboneto
lamellarboneoccurs.
•Underneaththeperiosteum,compactbone
forms
•Insidetheendosteum,cancellousboneforms.
•Bone developsfrommembranous
mesenchymalcell-Intramembranous
ossification.
22Physiology of bone formation_V.Mythily,JCE

23. Endochondral Ossification
•Inendochondralossification,bonedevelops
byreplacinghyalinecartilage.Cartilagedoesnotbecome
bone.Instead,cartilageservesasatemplatetobe
completelyreplacedbynewbone.
•Endochondral ossification takes much longer than intra-
membranous ossification.Bones at the base of the skull
and long bones form via endochondral ossification.
•In a long bone, for example, at about 6 to 8 weeks after
conception, some of the mesenchymal cells differentiate
into chondroblasts (cartilage cells) that form the hyaline
cartilaginous skeletal precursor of the bones .
23Physiology of bone formation_V.Mythily,JCE

24. Endochondral Ossification
•Thiscartilageisaflexible,semi-solidmatrixproducedby
chondroblastsandconsistsofhyaluronicacid,
chondroitinsulfate,collagenfibers,andwater.Asthe
matrixsurroundsandisolateschondroblasts,theyare
calledchondrocytes.
•Unlikemostconnectivetissues,cartilageisavascular,
meaningthatithasnobloodvesselssupplyingnutrients
andremovingmetabolicwastes.Allofthesefunctions
arecarriedonbydiffusionthroughthematrixfrom
vesselsinthesurroundingperichondrium,amembrane
thatcoversthecartilage
24Physiology of bone formation_V.Mythily,JCE

25. Endochondral Ossification
•Asmoreandmorematrixisproduced,thecartilaginous
modelgrowinsize.Bloodvesselsintheperichondrium
bringosteoblaststotheedgesofthestructureandthese
arrivingosteoblastsdepositboneinaringaroundthe
diaphysis–thisiscalledabonecollar.
•Thebonyedgesofthedevelopingstructureprevent
nutrientsfromdiffusingintothecenterofthehyaline
cartilage.Thisresultsinchondrocytedeathand
disintegrationinthecenterofthestructure.
25Physiology of bone formation_V.Mythily,JCE

26. •Withoutcartilageinhibitingbloodvessel
invasion,bloodvesselspenetratetheresulting
spaces,notonlyenlargingthecavitiesbutalso
carryingosteogeniccellswiththem,manyof
whichwillbecomeosteoblasts.These
enlargingspaceseventuallycombineto
becomethemedullarycavity.Boneisnow
depositedwithinthestructurecreating
theprimaryossificationcenter
26Physiology of bone formation_V.Mythily,JCE

27. Endochondral Ossification
•Whilethesedeepchangesareoccurring,
chondrocytesandcartilagecontinuetogrowatthe
endsofthestructure(thefutureepiphyses),which
increasesthestructure’slengthatthesametime
boneisreplacingcartilageinthediaphyses.This
continuedgrowthisaccompaniedbyremodeling
insidethemedullarycavity(osteoclastswerealso
broughtwithinvadingbloodvessels)andoverall
lengtheningofthestructure.Bythetimethefetal
skeletonisfullyformed,cartilageremainsatthe
epiphysesandatthejointsurfaceasarticular
cartilage.
27Physiology of bone formation_V.Mythily,JCE

28. Endochondral Ossification
•Afterbirth,thissamesequenceofevents(matrix
mineralization,deathofchondrocytes,invasionofblood
vesselsfromtheperiosteum,andseedingwith
osteogeniccellsthatbecomeosteoblasts)occursinthe
epiphysealregions,andeachofthesecentersofactivity
isreferredtoasasecondaryossificationcenter.
•Throughoutchildhoodandadolescence,thereremainsa
thinplateofhyalinecartilagebetweenthediaphysisand
epiphysisknownasthegrowthorepiphysealplate.
Eventually,thishyalinecartilagewillberemovedand
replacedbybonetobecometheepiphysealline.
28Physiology of bone formation_V.Mythily,JCE

29. Endochondral Ossification
•Endochondral ossification follows five
steps. (a) Mesenchymal cells
differentiate into chondrocytes that
produce a cartilage model of the future
bony skeleton. (b) Blood vessels on the
edge of the cartilage model bring
osteoblasts that deposit a bony collar.
(c) Capillaries penetrate cartilage and
deposit bone inside cartilage model,
forming primary ossification center. (d)
Cartilage and chondrocytes continue to
grow at ends of the bone while
medullary cavity expands and
remodels. (e) Secondary ossification
centers develop after birth. (f) Hyaline
cartilage remains at epiphyseal
(growth) plate and at joint surface as
articular cartilage.
29Physiology of bone formation_V.Mythily,JCE

30. Endochondral Ossification
•Mesenchymal cells-chondroblast-synthesise
cartillage matrix (Type II collagen& ground
substance)
•Matrix takes the shape of bone (hyaline
cartillage and chondrocyte in lacunae)
surrounded by perichondrium scaffolds.
•Chondrocytes in the centre of the bone like
structure-swell –hypertrophied
chondrocytes-develops vacuole.
30Physiology of bone formation_V.Mythily,JCE

31. Endochondral Ossification
•Hypertrophied chondrocytes-compress the
matrix-matrix calcifiacation occurs
•Part of the perichondrium in the middle of the
shaft becomes vascularized.
•This process change the perichondrium to
periosteum. chondrogenic cells to osteogenic
and forms osteoblast.
•Osteoblast –synthesize bony
matrix(subperiosteal bony collar)J
31Physiology of bone formation_V.Mythily,JCE

32. Endochondral Ossification
•Bonycollar–notallowschondrocytestoget
nourishment–hypertrophied–compressthe
cartillagematrix–chondrocytesdie-
•Osteoclast–digestthedeadchondrocytes
•Deadchondrocytesinthematrixformsspaces
inthematrixlinedwithcalcification
•Osteogenicbudformsbyosteoblast
infiltration.
32Physiology of bone formation_V.Mythily,JCE

33. Endochondral Ossification
•Osteogenicbudatthecentreofdiaphysis-
actasprimaryossificationcentre----allows
bloodvessels,haemopoieticcells,
osteoproogenitorcellsintomatrix
•osteoblastenterintolacunae–develops
immaturecancellousbone(mixtureof
calcifiedcartillage+calcifiedbones)
•Osteoclastsdestroytheportiontowards
thecentreformingmedullarycavity,
osteoblastlaydownbonearoundit
33Physiology of bone formation_V.Mythily,JCE

34. Endochondral Ossification
•This modelling extends towards epiphysis
•Thickening of bone collar and replacement of
cartillage with bone.
•Epiphyseal ends develop secondary
ossification centres.
•Oseoblast-osteoid-calcified –immature
woven-lamella.
34Physiology of bone formation_V.Mythily,JCE

35. Endochondral Ossification
•Hyaline cartilage
‘bones’ are
infiltrated with
blood vessels &
osteoblasts.
•Formation of
periosteum
•‘Collar’ of compact
bone around
diaphysis
35Physiology of bone formation_V.Mythily,JCE

36. Endochondrol Ossification
36Physiology of bone formation_V.Mythily,JCE

37. Endochondrol Ossification
37Physiology of bone formation_V.Mythily,JCE