L11: Catrilage, Specialised Connective Tissue & ECM

Question 1

What is the main implication of connective tissue having reduced cellular content in comparison to other connective tissue?

Answer 1

The ECM is the main stress bearing componenet, so forms an indirect means of cell/cell contact

Question 2

What are the 3 main types of cartillage and where can they be found?

Answer 2

• Hydraline: found in ribs, nose, articular joints (precursor for bones)
  defined by presence of indigenous chondrocytes
• Fibro: joint capsules, ligaments
• Elastic: ear, epiglottis, larynx

Question 3

What are the 2 key components found in articular cartillage?

Answer 3

Collage (type II) and aggrecan, which are important for strength and support

Question 4

What can loss of collagen integrity result in, with a named example?

Answer 4

The loss of strength of the matrix e.g. Ehlers Danos syndrome

Question 5

How do PGs attract water?

Answer 5

Their GAG content makes them highly charged

Question 6

PG attracts water and forms a hydrated gel. What is the purpose of this gel?

Answer 6

• provides resistance to compression
• results in swelling pressure (turgor)
• provides strength and support

Question 7

Adult cartillage only contains one type of PG, what?

Answer 7

Chondrocytes making only 5-10% in ECM volume

• they are large and mature cells in group 2-8 cells
• rich in RER and golgi secreting, high amounts of type II collagen and aggrecan

Question 8

What is the function of chondrocytes?

Answer 8

Differentiate during embryonic development from MSC to secrete components that establish the ECM (that is cartillage)

Question 9

What are MSCs (mesencyhmal stem cells)?

Answer 9

Cells that can differentiate into cartillage and bone

- some cartillage cells can also rerote into bone cell development, called osteoblasts

Question 10

What role do MSCs that differentiate into chondrocytes in transciptional signature?

Answer 10

• expression of Sox-9 (HMG-box DNA binding transcriptional factor) leads to Col2A expression

Question 11

What chondrocyte proliferation and ECM synthesis require?

Answer 11

TGF- beta, fibroblast growth factor (FGF), insulin like growth factor (IGF-1) and parathyroid hormone related protein (PTHrP)

Question 12

What is produced as a result of ‘spatial’ chondrocyte proliferation and ECM synthesis?

Answer 12

The ‘cartilage model’ forms during embryonic development

Question 13

What is ossification?

Answer 13

Where the cartillage model is replaced with bone

- cartillage is required for the production of osteoblasts as we go through development

Question 14

What orchestrates spatial patterning (location)?

Answer 14

Morphogens (secreted signalling molecules) via inductive signalling

• now cells can go into new developmental pathway
• inductive signalling requires morphogens passing down between cells through developing ECM

Question 15

What 2 key molecules are involced in inductive signalling?

Answer 15

1. Indian hedgehog (IHH): controls the production of the key skeletal morphogen
2. PTHrP

Question 16

How are IHH and PTHrP involved in inductive signalling?

Answer 16

Both are linked and act as a +ve feedback loop that maintains spatial chondrocyte proliferate

Question 17

Explain the function of the molecule ‘hedgehog’

Answer 17

Its a secreted morphogen which interacts with 2 receptors (patched+smoothened)
- this keeps the proteolytic processing of cobitus interruptus (Ci) turned off so it can move to nucleus and activate gene expression

Question 18

Explain the function of PTHrP in inductive signalling

Answer 18

PTHrP binds to G protein coupled receptor, turning on more genes and PTHrP and IHH, creating the +ve feedback loop
- also maintains chondrocyte proliferation and cartilage production & prevents their terminal differentiation

Question 19

What happens when formation of long bones from cartillage model is intitiated?

Answer 19

Cartillage in primary ossification centres are catabolised and osteoid ECM becomes calcified, trapping osteoblasts

Question 20

How are cartillage and long bone formation tightly linked during development?

Answer 20

By chondrocytes, osteoblasts and osteocytes

Question 21

How do proliferating cells contribute to the ossification process?

Answer 21

• as proliferating cells move further away from central cells, these start to receive less PTHrp and this also reduces IHH
• so cells make less PTHrP and become more osteoblast-like

Question 22

What is articular cartillage?

Answer 22

Connective tissue ECM that directs bone development during embryogenesis

• it’s essential for permitting mechanical load and movement of articulated bones
• contans only chondrocyes