Bone Formation Flashcards
Define intramembranous ossification.
Bone forms DIRECTLY within a membrane of highly vascular mesenchyme
What bones grow by intramembranous ossification?
Flat bones
Ex: flat bones of skull and face, the mandible, clavicle etc…
What do osteoprogenitor cells differentiate into? and where did they come from?
Osteoprogenitor cells differentiate into osteoblasts
Mesenchymal cells differentiate into osteoprogenitor cells
Are osteoblast basophilic or acidophilic?
Basophilic
What do osteoblasts synthesize?
organic components of the bone matrix: OSTEOID
What does osteoid consist of?
Proteins (collagen), proteoglycans with GAG side chains, and glycoproteins (osteonectin, sialoproteins, osteopontin, and osteocalcin)
What is the first bone laid down?
Primary (immature, woven) bone
How do the collagen fibers of primary bone appear?
Appear woven and are randomly oriented
*mostly type I collagen
What are spicules and trabeculae? What color do they stain?
- island-like structures floating in mesenchymal tissue, initial shape of primary deposited bone
- As they grow, they form the 3D framework
Spicules and trabeculae are esoinophilic and stain pink
How does the bone matrix “set”?
The soft osteoid of primary bone undergoes mineraliztion
When do osteoblasts become osteocytes?
After the mineralization of the bone matrix, osteoblasts become trapped in lacunae and are then referred to as osteocytes
How do osteocytes maintain contacts with other osteocytes?
cytoplasmic processes enclosed in CANICULI maintain contacts with the cytoplasmic processes of other nearby osteocytes
What is appostitional bone growth?
osteoblasts deposit bone matrix on the surface of existing spicules and trabeculae
How is primary bone replaced?
Primary bone is resorbed by OSTEOCLASTS and gradually replaced with secondary bone
How is secondary bone formed?
osteoblasts
Describe secondary bone.
mature, lamellar
What do newly formed bone spicules and trabeculae initially form?
spongy bone
The highly vascular connective tissue surrounding the bone spicules and trabeculae differentiates into bone marrow
How does spongy bone become compact bone?
via secondary deposition of bone tissue that fills in the marrow spaces
When does endochondral ossification begin?
12th wk of gestation
What is formed first in endochondral ossification? what happens to this structure?
A hyaline cartilage model of bone-to-be is formed first
It then becomes calcified, eroded, and replaced by bone
Which bones form using endochondral ossification?
Long bones of the limbs and vertebrae of the spine
Where is the primary ossification center located?
diaphysis
What signals the chondrogenic cells in the inner cellular layer of the perichondrium to differentiate? what do they differentiate into?
Vascularization of the perichondrium signals the chondrogenic cells to become osteoprogenitor cells
The perichodrium therefore becomes the periosteum
By what mechanism does the subperiosteal bony collar form?
new osteoblasts in the inner layer of periosteum synthesize and secrete bone matrix to build up the subperiosteal bony collar by INTRAMEMBRANOUS OSSIFICATION
What happens to the cartilage cells as the bony collar forms?
they hypertrophy (accumulate glycogen and form vacuoles)
How does the cartilage become calcified?
Hypertrophied cartilage cells produce alkaline phosphatase which calcifies the cartilage
Once the matrix is calcified, nutrients can no longer diffuse and the chondrocytes will die
(**note calcification of cartilage is not mineralization of bone*)
What forms perforations on the bone collar?
osteoclasts
What does a periosteal bud consist of?
blood vessels, osteoprogenitor cells, and hemopoietic stem cells
What happens to the remnants of the calcified cartilage?
osteoblasts form bone matrix (osteoid) on the remnants of calcified cartilage
Where is the secondary center of ossification located?
epiphysis
When do the secondary centers of ossification form?
One forms in the one epiphysis shortly after birth, the other forms in the other epiphysis shortly afterwards
How is bone formation in the epiphysis different from bone formation in the diaphysis?
epiphyses do not have a ‘bone collar’
Mnemonic for cartilage -> bone
CDER calcification death erosion replacement
Where is cartilage not replaced?
1) articular surfaces of the epiphyses
2) epiphyseal growth plates (allow long bones to grow until around age 21)
Describe long bone growth (in length)
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
[endochondral bone formation that occurs in the epiphyseal growth plates]
Does the thickness of the growth plate change as the bone grows?
No, but the distance between the growth plates does gradually increase
Name the zones in the epiphyseal plate starting at the epiphyseal side and progressing towards the diaphysis.
RPHCO “ruthless prince heckled combative ogres”
Reserve Cartilage Proliferation Hypertrophy Calcified Cartilage Resorption and Ossification
Which zone is “typical hyaline cartilage”?
Zone of reserve cartilage
mitotically active zone
In which zone do you see chondrocytes appearing in stacks, like multiple stacks of pennies?
Zone of proliferation
The stacks are parallel to the long axis of the bone
In which zone does intense mitosis take place?
Zone of proliferation
Cells here are multiplying and increasing in number
In which zone does cartilage grow interstially?
Zone of proliferation
Chondrocytes produce new organic matrix
In which zone do chondrocytes grow in size, but no new cell or matrix is formed?
Zone of hypertrophy
Chondrocytes accumulate glycogen and become vacuolated
The cells and lacunae enlarge at the expense of the matrix
In which zone do the chondrocytes die?
Zone of calcified cartilage
The lacunae coalesce and due to the calcification of the cartilage, chondrocytes die
In which zone would you find blood vessels bring ostoeprogenitor cells?
Zone of Resorption and ossification
osteoprogenitor cells emigrate to calcified cartilage matrix area and differentiate into osteoblasts
What is a “mixed spicule” and where would you find it?
A calcified cartilage/mineralized bone complex that would be found in the zone of resorption and calcification
How do you distinguish between calcified cartilage and mineralized bone?
With H&E staining
Calcified cartilage= basophilic= blue
-does not contain cells, will eventually be completely elilminated
Mineralized bone=acidophilic=pink
-contains living cells
Does the calcified cartilage of the diaphysis become bone?
NO
it doesn’t become bone- it is REPLACED by bone
Why does epiphyseal closure occur?
The growth in the zone of proliferation slows down, but the rate of ossification doesn’t and eventually the entire epiphyseal plate is replaced by bone
By what mechanism does bone growth in width occur?
Appositional growth via subperiosteal intramembranous bone formation
Describe subperiosteal intramembranous bone formation.
Osteoblasts depost bone on the external surface of bone.
Osteoclasts resorb bone on the internal surface of the bone.
The bone marrow cavity diameter increases and the bone diameter increases.
Where does mineralization of the bone occur?
osteoid
What are the seven steps to mineralization of bone?
1) Minerals are delivered by blood vessels to the forming bone.
2) Osteocalcin and other sialoproteins bind extracellular calcium.
3) The elevated concentration of calcium activates the osteoblasts to release alkaline phosphatase (ALP). ALP elevates local extracellular concentration of PO4 ions which also further elevate calcium.
4) Osteoblasts release matrix vesicles into bone matrix which regulate the initial site of mineral deposition in the osteoid.
5) The vesicle membranes contain pumps that transport more minerals into the vesicles.
6) Crystallization of the calcium and phosphate occurs in the vesicles, forming hydroxyapatite crystals (CaPO4).
7) The crystals damage the vesicle’s membrane and are deposited in the bone matrix.
What hormones does bone respond to?
Parathyroid hormone PTH and calcitonin
By what three mechanisms does bone repair occur?
intramembranous bone formation, cartilage formation and endochondral bone formation
Review the steps of bone repair listed in the handout.
Did you reread the steps?
What is the first cell to arrive at the site of bone injury?
neutrophils
What do macrophages do at the site of bone injury?
clean up debris
What do fibroblasts form at the site of bone injury?
granulation tissue (a LCT), later DCT and cartilage
What is the purpose of the soft callus? How is it formed?
The soft callus forms a bridge between the two bone fragments and covers the injured bone
It is formed by the granulation tissue and cartilage
Which type of bone re-forms first?
Spongy bone
the spongy bone will slowly be replaced by the compact bone
What is achondroplasia?
A genetic disorder (autosomal dominant or new mutation) of bone growth that causes the most common type of dwarfism
What causes the dwarfism seen in achondroplasia?
Decreased production of cartilage cells in the epiphyseal growth plates of long bones–> short bones in upper and lower limbs
What is seen histologically with achondroplasia in the epiphyseal growth plate zones?
Zones of proliferation and hypertrophy are slender and disorderly
Zone of proliferation lacks stacks of chondrocytes; chondrocytes present are enlarged and form clusters instead
What are some of the clinical presentations of achondroplasia?
midface hypoplasia large head with frontal bossing normal torso length lumbar lordosis short proximal upper and lower limbs bow legs short stature
