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Bone Development

Bone Development

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Published by: kkonci01 on Nov 03, 2009
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Bone Development, Modeling, and Repair 
1. Define and differentiate between endochondral and intramembranousossification.Endochondrial ossification
occurs within a hyaline cartilage model of the bone. The hyaline cartilage model in the shape of the bone is formed prior toany bone tissue being laid down. The cartilage is removed and then replacedwith bone tissue. The process occurs in two different places: during the initialdevelopment of the embryo/fetus and in the epiphyseal plate of a young child or adolescent. In the fetus, the process starts with a hyaline cartilage model of thebone. The first change occurs midshaft, where
hypertrophy
of chondrocyteshappens. The chondrocytes enlarge and secrete
alkaline phosphatase
. Thiscauses the cartilage matrix to calcify. The cartilage cells begin to die becausethe flow of nutrients is cut off by the hydroxyapetite crystals. At the same time asthe hyperatrophy of the chondrocytes, the
perichondrium
becomes active. Themesenchymal cells in the perichondrium differentiate into
osteoblasts
. Theosteoid (unmineralized bone matrix) is laid down by the osteoblasts. Thenmineralization of the osteoid can occur. This activity forms a
periosteal collar 
(subperiosteal bone collar) around the entire midshaft of the cartilage model.The bony collar is formed outside of the cartilage. The bony collar is formed by
intramembranous ossification
within the periosteum. Next, comes theinvasion of blood vessels in the form of 
periosteal buds,
which enter into thecartilage matrix via holes in the forming bone collar. The periosteal buds erodeaway the uncalcified cartilage matrix. These blood vessels bring inosteoprogenitor cells into the forming cavities in the cartilage matrix. The
osteoprogenitor cells
differentiate into osteoblasts. In order for this to happen,the osteoprogenitor cells migrate from the blood vessel to the surface of thecalcified cartilage matrix. The newly differentiated
osteoblasts
lay down osteoidon the surface of the remaining calcified cartilage matrix. The osteoblasts thenlay down new bone osteoid, layer by layer. Calcification of the bone osteoidbuilds up. This is always on the free surface of the cavity so it is
appositional
growth of bone.
Bone trabeculae
are formed with a center of calcified cartilage matrixsurrounded by bone tissue. The bone that is formed is spongy bone consistingof trabecula. This region is called
primary spongiosa
because it is the first areathat trabecular bone is formed. The bone first laid down here is
woven bone(immature)
due to its random organization of collagen fibers. If compactionoccurs (the spongy bone is converted into dense bone) the osteons formed willbe primitive osteons. The next step is
secondary bone formation
. This is doneby
internal remodeling
which removes the woven bone and replaces it withlamellar bone (mature). Endochondrial ossification is a continuous process thatstarts in the center of the bone and moves toward each end. The process startsat the
primary ossification center 
where ossification first appears in cartilagemodel. At the long bones of the body, this occurs in the center of diaphysis. A
secondary ossification center 
is where ossification begins anew in the samecartilage model of bone, but, in a different place after the primary ossification
 
center has started. In long bones, this is in the epiphysis. Irregular bones havemultiple ossification centers.
Ossification at the epiphyseal plate
occurs at the plate between the
diaphysis
and
epiphysis
of a long bone. The plate is made up of hyalinecartilage between the bone tissue of the two centers (a synchondroses cartilage joint). The plate is organized into fibe different zones. The
zone of reservecartilage
(resting zone) is located nearest to the epiphysis. It consists of normalhyaline cartilage and functions to attach cartilage to the bony epiphysis. The
zone of proliferation
is a region of rapid proliferation of chondroblasts. It isrecognized as columns of flattened cells that are really
isogenous groups
of chondroblasts originating from one stem cell. The ECM is slowly laid down toforce these cells apart. The zone of proliferation is the
interstitial growth
of thecartilage. This is key to the function of the plate. The
zone of maturation andhypertrophy
is where the chondrocytes round up and enlarge. This is due to theincreasing cell size as the matrix between cells in the column decreases. Thecells here begin to secrete
alkaline phosphatase
. The
zone of calcification
isa place where the cartilage matrix becomes mineralized. The amount of mineralbeing deposited in the matrix cuts off the nutrients and the cells die. It takesspecial calcium stains to visualize this zone so we can identify it by location. It isthe last two rows of enlarged cells adjacent to the resorption front. The
zone of ossification
is where the blood vessels invade into the cartilage matrix anderode it away. The
resorption front
is the same thing as the invasion zone.The dead chondrocytes and uncalcified cartilage matrix is removed.Osteoprogenitor cells are brought in with the invading blood vessels. Theymigrate across the space to the surface of the remaining cartilage matrix.Osteoblasts then differentiate on the surface of calcified cartilage matrix, layingdown bone osteoid on the cartilage surface. The osteoid is mineralized and thenew deposited bone is
woven bone
. The trabeculae tha tare formed are mostlylongitudinal in orientation. The bone typed formed here is spongy bone and it iscalled the
primary spongiosa
or 
zone of primary ossification
. The
zone of secondary ossification
is further away from the epiphyseal plate and not part of it. This is where internal remodeling takes place and the woven bone is replacedby lamellar bone.
Intramembranous ossification
starts in the vascular mesenchyme,where the pluripotential mesenchymal cells differentiate to form
osteoprogenitor cells
. The mesenchymal cells group together in the vascular mesenchyme.These cells then round up and make cellular contact with the adjacent cells. Bigthing to remember here are the many small blood vessels running through themesenchyme. When the O2 content is low, then cartilage is formed, O2 high,vascularized bone. The cells then secrete unmineralized organic bone matrixcalled
osteoid
. This pushes the cells further apart. The long cell processes stillmaintain contact with each other. Mineralization now occurs and forms small
bone islands
. As the mineralization progresses, the osteoblasts becomeembedded in the mineralized matrix to form osteocytes. The next generation of osteoblasts, comes from osteoprogenitor cells, differentiates and lines thesurface of the bone island to lay down the next layer of osteoid. The osteoblasts
 
come from the surrounding osteoprogenitor cells in the mesenchyme. Theseindividual bone islands increase in size by
appositional growth
. The separateislands enlarge until they touch to form
trabecula
. Appositional growthcontinues to enlarge the islands and lengthen the trabecula. This process is how
trabecular bone
(spongy) is first formed. Trabeculae are not straight, but followthe winding route of the blood vessels.
Compaction
is the formation of compactbone from spongy bone. This is simply a continuation of laying down new layersof osteoid and osteocytes on the surface of the trabecula. The result is the slowbuild up of the trabecula until the edges of the adjacent trabecula meet to form
primitive osteons
(made up of woven bone). This osteon may have concentricrings of osteocytes like a mature osteon. However, the new bone tissue is
woven bone (immature, primary bone)
. The collagen fibers (type I) are laiddown in interwoven bundles, not in the layers of parallel fibers as in lamellar bone. The skull bones are spongy bone until about 8 years old. They aregradually remodeled into
inner & outer tables
of compact bone. These layers of dense cortical bone are separated by a middle layer, the
diploe
, which consistsof spongy bone. Ossification starts in the center where the bone is going to form.The place where ossification starts for an individual bone is called the
ossification center 
. The ossification process starts in the center and radiatesout towards the periphery. Therefore, the oldest and most developed bone is inthe middle of the ossification center. You can see all the sequential steps of ossification by looking at a cross section of that ossification center. The mostmatrue bone is found in the center and the most immature is in the periphery.Remember that you have more than one ossification center in each bone.
2.Define and differentiate between bone formation and bone growth.
Bone formation is making new bone when nothing was originally there.Bone formation equals ossification which equals bone development. Bonegrowth is always appositional and involves getting larger through calcification andremodeling.
3.Describe what type of growth occurs in bone.
All bone growth is
appositional
. Osteoprogenitor cells differentiate intoosteoblasts; the osteoblasts lay down osteoid on the surface. Mineralization of osteoid occurs and osteoblast becomes osteocyte. This is all appositionalgrowth.
4.List and describe the steps of intramembranous bone formation.Intramembranous ossification
starts in the vascular mesenchyme,where the pluripotential mesenchymal cells differentiate to form
osteoprogenitor cells
. The mesenchymal cells group together in the vascular mesenchyme.These cells then round up and make cellular contact with the adjacent cells. Bigthing to remember here are the many small blood vessels running through themesenchyme. When the O2 content is low, then cartilage is formed, O2 high,vascularized bone. The cells then secrete unmineralized organic bone matrixcalled
osteoid
. This pushes the cells further apart. The long cell processes still

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