L11: Catrilage, Specialised Connective Tissue & ECM Flashcards
What is the main implication of connective tissue having reduced cellular content in comparison to other connective tissue?
The ECM is the main stress bearing componenet, so forms an indirect means of cell/cell contact
What are the 3 main types of cartillage and where can they be found?
- Hydraline: found in ribs, nose, articular joints (precursor for bones)
defined by presence of indigenous chondrocytes - Fibro: joint capsules, ligaments
- Elastic: ear, epiglottis, larynx
What are the 2 key components found in articular cartillage?
Collage (type II) and aggrecan, which are important for strength and support
What can loss of collagen integrity result in, with a named example?
The loss of strength of the matrix e.g. Ehlers Danos syndrome
How do PGs attract water?
Their GAG content makes them highly charged
PG attracts water and forms a hydrated gel. What is the purpose of this gel?
- provides resistance to compression
- results in swelling pressure (turgor)
- provides strength and support
Adult cartillage only contains one type of PG, what?
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
What is the function of chondrocytes?
Differentiate during embryonic development from MSC to secrete components that establish the ECM (that is cartillage)
What are MSCs (mesencyhmal stem cells)?
Cells that can differentiate into cartillage and bone
- some cartillage cells can also rerote into bone cell development, called osteoblasts
What role do MSCs that differentiate into chondrocytes in transciptional signature?
- expression of Sox-9 (HMG-box DNA binding transcriptional factor) leads to Col2A expression
What chondrocyte proliferation and ECM synthesis require?
TGF- beta, fibroblast growth factor (FGF), insulin like growth factor (IGF-1) and parathyroid hormone related protein (PTHrP)
What is produced as a result of ‘spatial’ chondrocyte proliferation and ECM synthesis?
The ‘cartilage model’ forms during embryonic development
What is ossification?
Where the cartillage model is replaced with bone
- cartillage is required for the production of osteoblasts as we go through development
What orchestrates spatial patterning (location)?
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
What 2 key molecules are involced in inductive signalling?
- Indian hedgehog (IHH): controls the production of the key skeletal morphogen
- PTHrP
How are IHH and PTHrP involved in inductive signalling?
Both are linked and act as a +ve feedback loop that maintains spatial chondrocyte proliferate
Explain the function of the molecule ‘hedgehog’
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
Explain the function of PTHrP in inductive signalling
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
What happens when formation of long bones from cartillage model is intitiated?
Cartillage in primary ossification centres are catabolised and osteoid ECM becomes calcified, trapping osteoblasts
How are cartillage and long bone formation tightly linked during development?
By chondrocytes, osteoblasts and osteocytes
How do proliferating cells contribute to the ossification process?
- 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
What is articular cartillage?
Connective tissue ECM that directs bone development during embryogenesis
- it’s essential for permitting mechanical load and movement of articulated bones
- contans only chondrocyes
