Osteogenesis from MSCs

Question 1

Give me 4 reagents that induce osteogenesis of MSCs

Answer 1

Dexamethosone
beta-glycerol phosphate
Ascorbate
BMP-2

Question 2

How do the reagents that induce osteogenesis of MSCs work?

Answer 2

Function to increase intracellular Runx2 levels either:
- directly (Dex, B-glycerol phostphate)
or indirectly (BMP)

Question 3

What is Runx2?

Answer 3

the major TF controlling osteo commitment and differentiation

Question 4

How does Runx2 carry out its function?

Answer 4

binds to the cis-element of osteocalcin gene which results in transcription of osteo genes

Question 5

Give me some examples of osteogenesis genes

Answer 5

Osteopontin
Osteocalcin
Alkaline phosphate (ALP)

Question 6

What is a recent discovery regarding Runx2 function and why is this thought?

Answer 6

thought to be key in TD from pre-adipose -> osteo as it:
decreases expression of adipo markers
increases expression of osteo markers

Question 7

What is osterix?

Answer 7

Osx = important Tf in osteogenesis that acts downstream of Runx2

Question 8

What is the evidence for osx’s function

Answer 8

Runx2 null mice = no Runx2 or Osx
Osx null mice = no Osx, normal Runx2
THEREFORE it must act downstream of Runx2

Question 9

What is the D1x family of tf’s and their function, paticular D1x5 and 3?

Answer 9

D1x = homeodomain TFs
5 = accelerates osteoblast differentiation in vitro
3 = promotes new bone formation and regulation of osteo differentiation

Question 10

At what stage in osteogenesis is Msx2 expressed?

Answer 10

It’s expressed in proliferating osteo precursors
but NOT differentiating cell types

Question 11

Why is Wnt signalling vital in Osteogenesis?

Answer 11

It’s vital for the commitment decision between osteo or adipo lineage as:
It inhibits PPARg
This prevents adipogenesis
Activates Runx2
This induces osteogenesis