Bone formation Flashcards
What is histogenesis?
Formation of bone
What are the two forms of histogenesis
intramembranous and endochondral ossification
What is intramembranous ossification?
The mechanism whereby bone forms directly within a membrane of highly vascular mesenchyme
What type of ossification does the skull, face, mandible, clavicle, and other flat bones form?
Intramembranous
True or false: Halversian canals are found exclusively in compact bone
True
Is osteoid a part of secondary or primary bone/
Secondary (early though, prior to mineral deposits)
What are the cells that form the primary bone in intramembranous ossification? Endochondral ossification?
Osteoblasts for both
True or false: spongy bone and compat bone are formed by two totally separate processes?
False– compact bone is formed from spongy bone
How does bone grow in intramembranous growth?
Appositional from the continued division of osteoprogenitor cells and changing into osteoblasts
How is primary bone replaced?
Via osteoclast re-absorption
What does bone form around?
Blood vessels
What is intramembranous ossification?
The process by which bone forms directly within a membrane of highly vascular mesenchyme
What is endochondral ossification?
A process by which a cartilage model of the bone-to-be is formed first, and then it becomes calcified, eroded and replaced by bone
When does endochondral ossification usually begin?
12th week of gestation
What type of cartilage is used in endochondral ossification?
Hyaline cartilage
What type of bones form from endochondral ossification? In what part of these bones does the ossification occur?
Long bones, within the diaphysis
What is hyaline cartilage formed from?
mesenchyme
Once the cartilage forms, how does it grow?
Both interstitailly and appositionally
What is the name of the cartilage that covers hyaline cartilage?
The perichondrium
What is the signal for chondrogenic cells in the inner layer of the perichondrium to differentiate?
Vascularization of the perichondrium
What are chondrogenic cells? What do they turn into in the perichondrium?
Mesenchymal cells that form into osteoprogenitor cells
What is the effect of the osteoprogenitor cells/osteoblats that they turn into, in the perichondrium?
Turn the perichondrium into a periosteum
What do the osteoblasts on the inner cell layer of the perichondrium form? What type of ossification is this (intramembranous or endocondrial)?
a bony collar, which is done via intramembranous ossification
As the bony collar of long bones form, what happens to the osteoblasts that were synthesizing the collar?
They hypertrophy via accumulation of glycogen
What do the hypertrophied osteoblasts near the bony collar secrete when they die? What is the function of this secretion?
They secrete alkaline phosphatase, which calcifies the matrix
True or false: calcification of cartilage = mineralization of bone (or very closely =)
False
What is the periosteal bud, and what is its function?
A structure consisting of blood vessels, osteoprogenitor cells, and hemopoietic stem cells.
Punches a hole in the collar of developing long bones (which is made up of dead cartilage cells), and allow for the formation of blood vessels within the collar
What allows for the in-growing of the periosteal bud? (what produces the holes)?
Osteoclasts
The osteoblasts on the periosteal bud form bone on what structure that is already present?
Form on the remnants of the calcified cartilage
Where are secondary ossification center? When do they form?
At the proximal and distal ends of long bones
These form shortly after birth
What is the only difference between bone formation in the primary and secondary ossification centers?
There is no bone collar formed in the secondary ossification center
How do the secondary ossification centers become ossified?
The cartilage cells die when they are too far from the perichondrium.
The osteoprogenitor cells come in from a bud, populate the calcified cartilage and differentiate into osteoblasts. These secrete bone.
The secondary ossification center produce bone in all but two places, which are what?
- Articular surfaces of the epiphyses
2. epiphyseal plates
Why is there no appositional growth at the articular surfaces? What kind of growth occurs here?
Because there is no perichondrium (you do not want to have fibrous cartilage develop here)
Interstitial growth occurs here.
How do long bones grow?
cartilage is continuously being replenished at the epiphyseal side of the growth plates and is concurrently replaced by bone at the diaphyseal side of the growth plates.
How does the thickness of the growth plate change as the bone grows?
Stays the same
How does the distance between growth plates change as the bone grows?
Increases
What are the zones of the epiphyseal plate (starting at the epiphyseal side and progressing toward the diaphysis)?
Zone of reserve cartilage Zone of proliferation Zone of hypertrophy Zone of carlcified cartilage Zone or reabsoption and ossificaion
What is the zone of bone growth above the epiphyseal plate? What is in this area? Is it mitotically active?
- Zone of reserve cartilage
- Filled with hyaline cartilage
- Small amount of mitosis
What is the zone that sit beneath the zone of reserve cartilage? What is the function of this area?
Zone of proliferation, where intense mitosis takes place and chondrocytes proliferate
How do the isogenous groups of chondrocytes appear at in the zone of proliferation?
Like stacked pennies, parallel to the long axis of the bone
What do the isogenous groups of chondrocytes at the zone of proliferation secrete?
They lay down hyaline cartilage matrix
How does cartilage grow in the zone of proliferation?
Interstially
What is the zone that is just below the zone of proliferation? What happens in this area? How much mitosis occurs here.
The zone of hypertrophy, where chondrocytes swell (vacuolate) and die. Thus no mitosis here
What do the cells in the zone of hypertrophy secrete? What is the consequence of this?
Secrete alkaline phosphatase, which causes the cartilage to calcify. This leads to cell death d/t lack of nutrient flow.
What is the zone of the growth plate that sits below the zone of hypertrophy? What occurs in this area?
The zone of calcification.
This is where lacunae coalesce, the matrix is calcified, and chondrocytes die.
What is the zone that sits below the zone of calcified cartilage? What occurs here?
The Zone of Resorption and Ossification.
This is where osteoprogenitor cells emigrate to via migrating blood vessels, and differentiate into osteoblasts
What is in the zone of resorption and ossification that osteoblasts form bone around?
spicules in the direction of the diaphysis
When staining with H&E, how does calcified cartilage appear? What will eventually happen to the calcified cartilage?
Blue (basophilic) without cells. This eventually become eliminated
When staining with H&E, how does mineralized bone appear? What will eventually happen to the calcified cartilage?
Acidophilic with living cells.
True or false: it is normal for both bone and cartilage to be mineralized
False–cartilage should not be mineralized
What are the cells that are on the surface of the calcified cartilage in the zone of calcification?
Osteoblasts.
What happens to the calcified cartilage/mineralized bone complex in the diaphysis?
Osteoclasts breakdown the calcified cartilage/mineralized bone complex, hollowing the bone marrow cavity.
What happens to the area of calcified cartilage of the diaphysis after the cartilage has been broken down?
It is replaced by bone
What happens in the closure of the growth plates?
The zone of proliferation slows down, and the zone of calcification catches up until it is entirely replaced by bone
How does bone growth in width?
Appositionally, with osteoblasts of the inner cell layer of the periosteum secreting bone matrix on the subperiosteal bone surface.
Osteoclasts absorb bone in the internal surface
How does osteoid become mineralized (5)?
- Minerals are delivered by blood vessels to forming bone,
- osteocalcin and silaoproteins bind to Ca.,
- ALP increases to increase extracellular PO4, which increase Ca more
- Osteoblasts release vesicles with Ca into the bone matrix
- Pumps fill the vescile with more ions, until hydoxyapatite crystals cause it to pop, inside the bone matrix
When looking at an epiphseal plate, how can one determine which side is the diaphysis, and which is the epiphysis?
Diaphysis will stain red due to collagen 1 (bone), whereas the epiphysis side will stain blue
At about what age do the epiphyseal plates close?
20
What would happen if there was insufficient osteoclacin or sialopriotins in the osteoid?
Not enough Ca would be absorbed from the blood to calcify the matrix.
What is the protein that helps glue the hydroxyapatite crystals to collagen?
Osteonectin
In bone remodeling, where does bone deposition vs resorption occur?
Deposition on the outer surface; resorption on the inner surface
What is the hormone that regulates bone resorption/deposition
Parathryoid hormone (PTH) and calcitonin
After the blood supply is disrupted and cells in the bone matrix die, what arrives to begin the process of healing?
Neutrophils and macrophages to clean up site of injury
What is the part of bone healing that occurs after macrophages and neutrophils have cleaned up the site of injury?
Granulation tissue forms from fibroblasts, forming a soft callus to cover the injured bone
What is a soft callus?
granulation tissue that covers the site of an injured bone, and helps form a bridge between the two broken bones
What happens in bone repair after the soft callus forms?
osteoprogenitor cells in the periosteum divide and differentiate to form osteoblasts, which synthesize osteoid.
What happens in bone repair after the osteoprogenitor cells form osteoblasts?
Osteogenic buds form, cartilage calcifies, dies, and is replaced by bone, forming a bony callus
What happens at the same time the bony callus forms in bone repair?
Endosteal proliferation results in bone spicules to grow toward the marrow cavity, forming spongy bone that is later replaced by compact bone
What happens as the spongy bone is being replaced by compact bone in bone repair?
bony callus is broken down by osteoclasts, and bone is remodeled to original shape
What is the cause of achondroplasia?
cartilage in the growth plates is replaced by bone at a very slow rate resulting in short bones in the upper and lower limbs. Specifically, the zones of proliferation and hypertrophy are slender and disorderly
What would you expect to see in a sample of a growth plate in a patient with achondroplasia?
The zone of proliferation lacks stacks of chondrocytes and the chondrocytes present are enlarged and form clusters instead.
In secondary ossification centers, how does bone grow in width? In length?
Length = interstitial growth Width = appositionally
What is the signal for the perochondrium to turn into periosteium?
Vascularization (NOT from the periosteal bud)
What happens to the chondrocytes as the bone collar is formed?
They die d/t calcification of their surrounding space
