201 L2

Question 1

What is the perichondrium?
How many layers does it have?
What are the functions of the layers?

Answer 1

A layer of CT that surrounds the cartilage (except for articular cartilage).
Outer fibrous layer for protection
Inner layer where cartilage progenitor cells are that differentiate into chondroblasts, then chondrocytes.

Question 2

Where are chondrocytes located and what are they in?

Answer 2

Located in the ECM in cavities called lacunae.

Question 3

what happens to the lacunae as the progenitor cartilage cells mature?

Answer 3

The lacunae become more rounded.

Question 4

What is the function of the chondrocytes?

What type of growth do they perform?

Answer 4

They divide within the lacunae and start depositing matrix between them.
Interstitial growth.

Question 5

What type of cartilage is describe below:

Provides stiff but flexible support. Reduces friction between bony surfaces.

Answer 5

Hyaline Cartilage

e.g. trachea

Question 6

What type of cartilage is describe below:

Provides support, but tolerates distortion without damage and returns to original shape.

Answer 6

Elastic cartilage

e.g. top of ear

Question 7

What type of cartilage is describe below:

Resists compression, prevents bone to bone contact, limits relative movement.

Answer 7

Fibrous Cartilage

e.g. Intervertibral discs, pads between knee joints

Question 8

Elastic cartilage is composed of elastic fibres which provides the cartilage with more ———- and ——–

Answer 8

Resistance and flexibility

Question 9

Fibrous cartilage is composed of ——— fibres packed like in —— CT proper making it —— and —— to ——-

Answer 9

Fibrous cartilage is composed of collagen fibres packed like in dense CT proper making it tough and resistant to compression.

Question 10

The matrix of bone is ——-

Answer 10

Calcified

Question 11

Bone is highly ———-

Answer 11

Vascularised

Question 12

Compact bone
Has concentric ———— which is formed when —— is laid down to form layers. These form circles around —— ——- forming ———.
———– lamellae are found in between the ———.
———— lamellae surround the ——- structure all together.
Within the osteon there are ——- that have ——– in them.
The ——– are connected by ———, which have projections that allow ———— between each other.
The ———- is outside the ——– lamellae.

Answer 12

Compact bone
Has concentric lamellae which is formed when ECM is laid down to form layers. These form circles around blood vessels forming osteons.
Interstitial lamellae are found in between the osteons.
Circumferential lamellae surround the bone structure all together.
Within the osteon there are lacunae that have osteocytes in them.
The lacunae are connected by canaliculli, which have projections that allow communication between each other.
The periostium is outside the circumferential lamellae.

Question 13

Where is the periostium?

Answer 13

Outside the circumferential lamellae

Question 14

What are the layers of the periostium?

Answer 14

Outer fibrous layer of CT proper

Inner layer with osteoprogenitor cells that give rise to more bone cells.

Question 15

What are the types of bone?

Answer 15

Non-lamellar (woven bone)

lamellar - Spongy or Compact bone

Question 16

Non-lamellar bone is also known as —— bone. It is ——- bone and is found in ——– and during bone —– and ——.

Answer 16

Non-lamellar bone is also known as woven bone. It is immature bone and is found in foetus and during bone remodelling and repair.

Question 17

Lamellar bone is also known as ——– bone. The lamella are mainly ——-. The shape of the bone is ——-.

Answer 17

Lamellar bone is also known as spongy/trabecular bone. The lamella are mainly parallel. The shape of the bone is irregular.

Question 18

Compact bone is about —–% of adult bone mass. The lamella are concentric ——–.

Answer 18

Compact bone is about 80% of adult bone mass. The lamella are concentric osteons.

Question 19

Eventually trabecular (spongy) bone starts remodelling to form ——— bone. So in the ——— you would have —— ——- and the trabecular would start to grow ———- the ——— due to the actions of ———- (reabsorb the bone)

Answer 19

Eventually trabecular (spongy) bone starts remodelling to form compact bone. So in the marrow you would have blood vessels and the trabecular would start to grow around the vessels due to the actions of osteoclasts (reabsorb the bone)

Question 20

What is trabecular bone embedded in?

Answer 20

Embedded in cavities filled with bone marrow

Question 21

What are the 3 germ layers?

Answer 21

Ectoderm
Mesoderm
Endoderm

Question 22

From what germ layer do most skeletal structures arise from

Answer 22

Mesoderm layer

Question 23

The endoskeleton of vertebrates is composed mainly of ——–

Answer 23

Bone

Question 24

What is the endoskeleton made up of?

Answer 24

Bone
Persistent cartilage
Replacement cartilage

Question 25

What is the origin of the axial skeleton?

Answer 25

The sclerotome of the embryonic somites

Question 26

What is the origin of the limb skeleton?

Answer 26

Lateral plate mesoderm

Question 27

What is the origin of the head?

Answer 27

Cephalic mesoderm

Cranial neural crest

Question 28

The ———– region of the somites give rise to ——– cells.

Answer 28

The sclerotome region of the somites give rise to bone cells.

Question 29

What is the cartilage called that transforms into bone?

Answer 29

Replacement cartilage

Question 30

What is the cartilage called that remains as cartilage?

Answer 30

Persistent cartilage

Question 31

Why is a pre skeleton that is made of cartilage advantageous?

Answer 31

Because the cells in the inside and outside of cartilage can grow it is easier to model the shape of the skeleton and let it grow as the embryo grows in size.

Question 32

The process when bone forms without first going through a cartilage phase is called ——- ——- — —–.

Answer 32

Direct formation of bone

Question 33

What are mesenchymal cells?

Answer 33

Cells that are loosely packed and tend to migrate a lot.

Question 34

The ——— cells will position themselves in the places where ——- is going to need to be formed.

Once they get there they can either form —— or ——-, depending of the signals and interactions with the ——- ——-.

Answer 34

The mesenchymal cells will position themselves in the places where skeleton is going to need to be formed.

Once they get there they can either form bone or cartilage, depending of the signals and interactions with the circulatory system (blood).

Question 35

In the presence of ——– interactions with blood the mesenchymal cells ——– and transform themselves ——— into ———.

What is the process called?

Answer 35

In the presence of strong interactions with blood (+vasculature) the mesenchymal cells condense and transform themselves directly into bone (e.g. skull)

Intramembranous ossification

Question 36

When there are ——- ——- received from the blood, the mesenchymal cells ——– and transform into ———–.

Further on, some ——— continues to receive – —— from the blood system and become ———- ———-, while some ———- interacts with blood and becomes ——–.

The process when the ——– interacts with blood and becomes —— is called ——– ———-
What is this process called?

Answer 36

When there are no signals received from the blood (- vasculature) the mesenchymal cells condense and transform into cartilage. Further on, some cartilage continues to not receive signals from the blood system and become persistent cartilage, while some cartilage (replacement) interacts with blood and becomes bone.

The process when the cartilage interacts with blood and becomes bone is called endochondral ossification

Chondrogenesis

Question 37

What are the key steps in skeletogenesis?

Answer 37

Settlement of migrating cells
Formation of the matrix (collagen, fibronectin, hyaluronin)
proliferation and apoptosis of cells resulting in shaping the bone.

Question 38

What two cell types form mesenchymal cells?

Answer 38

Neural crest cells

mesoderm cells

Question 39

What are the two factors and their functions that regulate skeletogenesis?

Answer 39

Differentiation factors - Signals from the blood telling the cells to become cartilage or bone producing cells.

Patterning factors - regulate cell proliferation and apoptosis, shaping the skeleton for specific parts of the body.

Question 40

What are the two differentiating factors that are expressed by the mesenchymal cells?

Answer 40

Runx2 - bone linage

Sox9 - cartilage linage

Question 41

If Runx2 is expressed in the immature ———– cells the ———– mesenchymal cells will become ——–.

Runx2 is expressed in the mesynchemyal cells that will make up the ——- —– and most of the —— —– skeleton

Answer 41

If Runx2 is expressed in the immature mesenchymal cells the condensed mesenchymal cells will become bone.

Runx2 is expressed in the mesynchemyal cells that will make up the cranial vault and most of the upper facial skeleton.

Question 42

If Sox9 is expressed in the immature ——- cells the ——— mesenchymal cells will become ———–.

Sox9 is expressed in the mesynchemyal cells that will make up the ——– and —— skeleton and also the base of the ——.

Answer 42

If Sox9 is expressed in the immature mesynchemyal cells the condensed mesenchymal cells will become cartilage.

Sox9 is expressed in the mesynchemyal cells that will make up the appendicular and axial skeleton and also the base of the skull.

Question 43

Runx2 is the main ———– factor that stimulates ———.

Answer 43

Runx2 is the main osteogenic factor that stimulates osteogenesis.

Question 44

What cells express Runx2?

Answer 44

skeletogenic cells

Question 45

Runx2 remains expressed in differentiating —— until maturation into ——-.

Answer 45

Runx2 remains expressed in differentiating osteoblasts until maturation into osteocytes.

Question 46

What other factor other than Runx2 is needed to form bone?

Answer 46

Ostrex

Question 47

What is the function of osterix?

Answer 47

It represses the chondrocyte fate of skeletogenic cells (stops cell from becoming a cartilage cell)

It ensures osteoblast differentiation of Runx2 positive osteogenic cells.

Question 48

Osteogenesis (ossification) always starts with the formation of ——— called ——— which is —- ——-.

Answer 48

Osteogenesis (ossification) always starts with the formation of ECM called osteoid which is non calcified.

Question 49

In both bone and cartilage the —— is formed first.

Answer 49

Osteoid

Question 50

What are the types of bone growth and development?

Answer 50

Intramembranous ossification

Endochondral ossification

Question 51

What form of ossification is described below:

Once ———–cells differentiate into ———-, they start depositing a —— ——, which will later become ——-.

The first ——- that is laid down is always ———- bone, followed by ——– bone.

Continued ——- secretion, ———— and ———- growth leads slowly to the fusion of neighbouring ossification centres, trapping ——- ——- and eventually the formation of ——– ——-.

This process is called —— ——–.

Answer 51

Once mesynchymal cells differentiate into osteoblasts, they start depositing a bone matrix, which will later become calcified.

The first bone that is laid down is always woven bone (immature - no lamellae), followed by trabecular bone (parallel lamella).

Continued matrix secretion, calcification and trabecular growth leads slowly to the fusion of neighbouring ossification centres, trapping blood vessels and eventually the formation of compact bone.

This process is called intramembranous ossification

Question 52

The centre of condensation in cartilage forms as cells condense and ———- into ———.

Differentiation of ———- starts at the centre of condensation and then spreads to the ———.

A few layers of ———- cells remain on the outside to form the embryonic —————, where they express ——— factors and give rise to new ——- and ———- for ———- growth

Answer 52

The centre of condensation in cartilage forms as cells condense and differentiate into chondroblasts.

Differentiation of chondroblasts starts at the centre of condensation and then spreads to the periphery.

A few layers of peripheral cells remain on the outside to form the embryonic perichondrium, where they express patterning factors and give rise to new chondroblasts and chondrocytes for appositional growth.

Question 53

What are the 2 steps in the formation of cartilage?

Answer 53

Precartilagenous condensation

Chondrocyte early differentiation

Question 54

In step 1 of the formation of cartilage, ————- ———-, the ————– cells stop ———– and start expressing type 1 ——–, ———, - —— and other ——– proteins that allow them to tightly aggregate.

In step 2, ———- —– ———, the condensed cells undergo early chondrocyte differentiation, stop expressing ——— molecules, resume ———- and start producing cartilage ——.

Answer 54

In step 1 of the formation of cartilage, precartilaginous condensation, the skeletogenic cells stop proliferating and start expressing type 1 collagen, hyaluronan, N cadherin and other adhesion proteins that allow them to tightly aggregate.

In step 2, chondrocyte early differentiation, the condensed cells undergo early chondrocyte differentiation, stop expressing adhesion molecules, resume proliferation and start producing cartilage ECM.

Question 55

The mesenchymal condensations are partitioned into:

A region that will form the ———- ———— of articulation

Regions that will form ——— ————- that will transform into ——-.

Answer 55

The mesenchymal condensations is partitioned into:

A region that will form the PERSISTENT CARTILAGE of articulation

Regions that will form REPLACEMENT CARTILAGE that will transform into bone

Question 56

What prevents the formation of cartilage to bone in relation to blood vessels?

Answer 56

The ECM/cartilage secretes angiorepellent signals that repel blood vessels, preventing the formation of bone.

Question 57

Briefly describe the steps of endochondral ossification?

Answer 57

Mesenchymal cells become committed to becoming cartilage

Committed mesenchymal cells condense and differentiate into cartilage

Chondrocytes proliferate forming the skeletal model for bone

Chondrocytes become hypertrophic and begin to calcify the matrix and then die.

Blood vessels enter and bone is formed

Question 58

What causes the chondrocytes to become hypertrophic?

Answer 58

Nutrients can only reach the chondrocytes through diffusion so as the skeleton grows the chondrocytes become hypertrophic (key to the formation of bone) and begin to calcify the matrix so they can’t get any nutrients anymore and they die.

Question 59

Complete the description of the final stage of endochondral ossification below:

Now that the ———— are dead the ———— signals that were sent to the blood circulatory system are —– being sent so —– ——– move —-, bringing ————– cells which replace the ————- cells and the formation of ——– bone begins.

Eventually the bone transforms into ———- bone through the remodelling of ———– fibres into layers.

As the ———– bone grows the components around the bone become ——— inside the bone being formed. This results in the formation of —— bone with ——– lamellae.

Answer 59

Now that they are dead the repulsive signals that were sent to the blood circulatory system are no longer being sent so blood vessels move in, bringing osteoprogenitor cells which replace the chondroprogenitor cells and the formation of woven bone begins.

Eventually the bone transforms into trabecular bone through the remodelling of collagen fibres into layers.

As the trabecular bone grows the components around the bone become trapped inside the bone being formed. This results in the formation of compact bone with concentric lamellae.

Question 60

What do hypertrophic chondrocytes do?

Answer 60

They modify the ECM so it can be mineralised

They may secrete VEGF to induce blood vessel formation (as a result of deprived oxygen?)

Question 61

Formation of long bones through endochondral ossification

1. Chondrocytes in the centre of the cartilage become ———. The ————- chondrocytes modify the ——– so it can be ———–. The outer parts of the bone are still ——— so it’s surrounded by ———.
2. Hypertrophic chondrocytes may secrete —— to induce —— —— formation. When —— ——- grow around the edges of the ———- the cells of the ———– convert to ——–. A bony —— is formed around the ——– of the ———, forming the ———— which then starts contributing to bone formation. The ——— is still surrounded by ———-.
3. ——- ——– penetrate the cartilage and enter into the holes left by ———– that have died in the ———-. The blood vessels carry ——— cells to the primary ———– centre. Mature ——- begin to form —- in the degrading cartilage ——–.
4. ———— come in & degrade the bone matrix. ———- & ———- remodel the bone. While bone is forming the ———– are trapped. The growth plates are formed which provide a continuous source of ——— for long bones. End up with a ——— diaphysis, ——- bone on the outside and ——– bone on the inside.
5. ———– and ———- migrate into the ———, creating secondary ossification centres. The same process happens in the epiphysis. ——— of chondrocytes and ———- of cartilage ———-. Invasion of ——- ——. Invading ——— form the bone matrix. Resorption by ———.
6. The ——- is filled with ——- bone. All the ———- has transformed to ———–, except for at the tips where it is lost and ——- cartilage is formed. ——— plates have formed.

Answer 61

1. Chondrocytes in the centre of the cartilage become hypertrophic. The hypertrophic chondrocytes modify the ECM so it can be mineralised. The outer parts of the bone are still cartilage so it’s surrounded by perichondrium.
2. Hypertrophic chondrocytes may secrete VEGF to induce blood vessel formation. When blood vessels grow around the edges of the cartilage the cells of the perichondrium convert to osteoblasts. A bony collar is formed around the outside of the diaphysis, forming the periosteum which then starts contributing to bone formation. The epiphysis is still surrounded by periochondrium.
3. Blood vessels penetrate the cartilage and enter into the holes left by chondrocytes that have died in the diaphysis. The blood vessels carry pre-osteogenic cells to the primary ossification centre. Mature osteoblasts begin to form bone in the degrading cartilage matrix.
4. Osteoclasts come in & degrade the bone matrix. osteoblasts & osteoclasts remodel the bone. While bone is forming the capillaries are trapped. The growth plates are formed which provide a continuous source of cartilage for long bones. End up with a hollow diaphysis, compact bone on the outside and spongy bone on the inside.
5. capilleries and osteoblasts migrate into the epiphysis, creating secondary ossification centres. The same process happens in the epiphysis. Hypotrophy of chondrocytes and mineralisation of cartilage matrix. Invasion of blood vessels. Invading osteoblast form the bone matrix. Resorption by osteoclasts.
6. The epiphysis is filled with spongy bone. All the perichondrium has transformed to periosteum, except for at the tips where it is lost and articular cartilage is formed. Growth plates have formed.

Question 62

Organisation of Cartilage within epiphyseal plate of growing long bone.

Resting zone
This is ——- cartilage
——— are spherical & separated by large amounts of ——–.
Cells from this zone eventually become arranged into regular columns forming the zone of ————.

Zone of proliferation
Chondrocytes begin to rapidly ——- laying down new ——- & forming columns of ——- cells.

———– is maximum and hence this part is mainly the one that contributes to bone ————.

The chondrocytes become pre- ———–.

Zone of hypertrophy and calcification
There are — ———- chondrocytes

Growth in this zone is due to an increase in —— of the chondrocytes.

In the midsection, chondrocytes become ———– and the ——- between them becomes ———.

Zone of cartilage degeneration
Chondrocytes die because they are deprived of ——- by the ——— matrix, and undergo ———- leaving behind a ——– that is empty.

Osteogenic zone

Empty lacunae are invaded by ————- cells which enter the degenerated cartilage with ————-.

The osteoblasts lay down —— on the surface of the ——— matrix, which then calcifies into ——– bone.

———– reabsorb the ——- bone and ———– replace it with ———– bone, completing endochondrial ossification.

Cavities left behind merge to become the ——— cavity

Answer 62

Resting zone
This is hylaine cartilage
Chondrocytes are spherical & separated by large amounts of matrix.
Cells from this zone eventually become arranged into regular columns forming the zone of proliferation.

Zone of proliferation
Chondrocytes begin to rapidly divide laying down new matrix & forming columns of stacked cells.

Proliferation is maximum and hence this part is mainly the one that contributes to bone lengthening.

The chondrocytes become pre- hypertrophic.

Zone of hypertrophy and calcification
There are pre-hypertrophic chondrocytes

Growth in this zone is due to an increase in size of the chondrocytes.

In the midsection, chondrocytes become hypertrophic and the matrix between them becomes calcified.

Zone of cartilage degeneration
Chondrocytes die because they are deprived of nutrients by the calcified matrix, and undergo apoptosis leaving behind a lacuna that is empty.

Osteogenic zone
Empty lacunae are invaded by osteopregenitor cells which enter the degenerated cartilage with capilleries.

The osteoblasts lay down osteoid on the surface of the calcified matrix, which then calcifies into woven bone.

Osteoclasts reabsorb the woven bone and osteoblasts replace it with spongy bone, completing endochondrial ossification.

Cavities left behind merge to become the medullary cavity

Question 63

Name the bone cells and their functions.

Answer 63

Osteocyte - Mature bone cell that maintains the bone matrix

Osteoblast - Immature bone cell that secrete organic matrix components.

Osteoprogenitor cells - Stem cell whose divisions produce osteoblasts.

Osteoclast - Multinucleate cell that secretes acids and enzymes to dissolve bone matrix

Question 64

Fomration of osteon

Growth in width happens through ———– growth of bone. This is when there is addition of bone
on the ———- surface, coupled with removal of bone from the ——– surface.

Beneath the ——— the osteogenic layer deposits — —-, as layers
around blood vessels.

The newly forming —- folds around the blood vessel, the ——- of the newly formed tube will be lined by ————- cells of the ——— and contain a blood vessel at its ———–.

As growth rate is ———, the ———– surface of the bone becomes flatter, and bone
becomes deposited as ——- that surround the entire —–.

Answer 64

Growth in width happens through appositional growth of bone. This is when there is addition of bone
on the periosteal (outside) surface, coupled with removal of bone from the endosteal (inside) surface.

Beneath the periostium the osteogenic layer deposits new bone, as layers
around blood vessels.

The newly forming bone folds around the blood vessel, the inside of the newly formed tube will be lined by osteogenic cells of the periosteum and contain a blood vessel at its center.

As growth rate is reduced, the periosteal surface of the bone becomes flatter, and bone
becomes deposited as lamallae that surround the entire bone shaft.

Question 65

Why are concentric lamellae formed?

Answer 65

Formed due to the orientation of the collagen fibres that have been laid down.

Question 66

The way that ——– ——- are laid down contribute to the resistance that bone has

Answer 66

collagen fibres