Cartilage tissue development

Question 1

Where does cartilage derive from?

Answer 1

Mesenchymal precursor cells from the lateral plate mesoderm

Question 2

Describe the formation of joints during embryogenesis

Answer 2

Prechondrocyte mesenchymal cells condensate to form tissue anlagen

Controlled apoptosis of chondrocytes within cartilage anlagen triggers the formation of joints

Question 3

What are interzones?

Answer 3

Thin mesenchymal cell layer forming at future joint sites

Question 4

What determines the longitudonal growth of long bones?

Answer 4

Growth plates

Question 5

What stops growth of long bones during adulthood?

Answer 5

Mineralisation of the growth plate

Question 6

Structure of the growth plate

Answer 6

Chondrocytes arranged in columns that parallel the axis of the bone

Question 7

What is the primary zone of the growth plate?

Answer 7

Consists of undifferentiated chondrocyte progenitors

Zone found closest to the epiphyseal end

Question 8

What are other names for the primary zone of the growth plate?

Answer 8

Resting or germinal zone

Question 9

Characteristic of resting zone of the growth plate not observed in the rest of the growth plate

Answer 9

Chondrocytes of the resting zone are distributed sporadically and have a low rate of proliferation

Question 10

How do chondrocytes coordinate longitudonal growth ?

Answer 10

Chondrocytes move out from the resting zone

Gain proliferative phenotype

Adopt a flattened oblate shape

Arrange themselves into longitudonal columns

Undergo a period of high secretory activity as they secrete ECM

Undergo maturation - gradually become hypertrophic (WNT and BMP)

During maturation chondrocytes decrease expression of collagen type II

Mature chondrocyes start to express collagen type X

Death of hypertrophic chondrocytes due to restriction of nutrients

Calcified matrix invades further down the diaphysis

Osteoclasts erode the newly deposited matrix and osteoblasts secrete more calcified matrix => ossification zone

Question 11

What controls the high mitotic activity of proliferating chondrocytes which move from the resting zone ?

Answer 11

Endocrine and autocrine regulation

Circadian rhythm

Age

Question 12

What type of matrix do these proliferating chondrocytes make?

Answer 12

Matrix rich in collagen type II and proteoglycan

Resembles the articular cartulage ECM

Question 13

What are the 3 phases through which mammalian chondrocyte volume increases?

Answer 13

True hypertrophy

Cell swelling

Second distinct phase of true hypertrophy

Question 14

Characteristics of true hypertrophy

Answer 14

Increase in dry mass production

Increase in fluid uptake

Responsible for threefold increases in volume

Question 15

How much does cell swelling contribute to chondrocyte volume increase?

Answer 15

Fourfold enlargement

Question 16

Which signalling pathway is essential during growth plate and articular cartilage function?

Answer 16

WNT pathway

Question 17

Which cells initiate the synthesis of collagen type-X?

Answer 17

Hypertrophic chondrocytes

Question 18

What indicates the final maturation phase of a chondrocyte?

Answer 18

Increased membrane activity of alkaline phosphatase

Question 19

What causes the mineralisation of the matrix?

Answer 19

Secretion of collagen type-X

Increased membrane activity of alkaline phosphatase

Question 20

When does longitudonal bone growth cease?

Answer 20

Once the growth plate closes when sexual maturity is reached

Question 21

What initiates the closing of the growth plate?

Answer 21

Formation of mineralised tethers betweeen epiphyseal and diaphyseal bone

Promotes the fusion of the primary and secondary ossification centers

Question 22

What happens to the chondrocytes of the growth plate when the growth plate closes?

Answer 22

Chondrocytes reach a state of sensescence

Because they exhaust their proliferative potential

Question 23

Which signalling pathways triggers the progression of prehypertrophic chondrocytes to hypertrophic chondrocytes?

Answer 23

BMP signalling

WNT signalling

Question 24

What is a columnar chondrocyte?

Answer 24

Chondrocytes that have moved out from the resting zone and gained proliferative phenotype

Arrange themselves into columns

Question 25

Role of columnar chondrocytes

Answer 25

Regulate cell proliferation of immature chondrocytes via Ihh feedback loop

Question 26

What are the roles of Ihh?

Answer 26

Converts perichondral cells to osteoblasts of the bone collar

Induces expression of PTHrP

Promotes chondrocyte proliferation

Regulates the transition from periarticular into columnar proliferating chondrocytes

Question 27

What is PTHrP?

Answer 27

Parathyroiod hormone related protein

Question 28

Which cells secrete PTHrP?

Answer 28

resting zone chondrocyes

Secrete the protein in response to activation by Ihh from prehypertrophic chondrocytes

Question 29

What is the role of PTHrP?

Answer 29

Keeps chondrocytes proliferating

Maintains cells in a premature state by suppressing hypertrophy

If less PTHrP present - chondrocytes go from prolifeating to hypertrophy

Question 30

What is the relationship between distance and PTHrP release?

Answer 30

Keeps chondrocytes proliferating

If less PTHrP = chondrocytes go from proliferating to hypertrophy

The greater the distance of the PTHrP signal, the more chondrocytes undergo hypetrophy and more Ihh released

Question 31

Which cells secrete Ihh?

Answer 31

Prehypetrophic chondrocytes

Question 32

What are the 5 zones of interstitial bone growth?

Answer 32

Zone of resting cartilage

Zone of proliferating cartilage

Zone of hypertrophic cartilage

Zone of calcified cartilage

Zone of ossification

Question 33

Which part of the bone has the resting zone?

Answer 33

Epiphyseal bone