Heparanase (Hpa1) Expression and its Function
in Bone Development
Dr. Cindy Farach-Carson
Dr. Daniel Carson
Factor
A
Factor
B
Factor
C
Cells
Tissues
Organs
How does this relate to my “science project”?
Heparan Sulfate
Proteoglycan
(HSPG) [Sugar Protein]
Growth
Factor and
Receptor
Molecule for
cleavage
Heparanase
(an enzyme)
Cells
Cartilage/Bone
Tissues
Organs
What molecules are important for bone
development and growth?
a trimolecular complex
Pz
PHz
Hz
PZ = proliferative zone
PHz= Prehypertrophic Zone
Hz= Hypertrophic Zone
Image modified from Miller et al., Differentiation (2003) 71:1-15
Heparanase-1 (Hpa-1), a member of the
trimolecular complex, expression in mouse
limb and chondrocytes
In vivo
A.
In vitro
B.
PHz
Pc
Hz
MT
RED: Perlecan GREEN: Hpa-1
BLUE:Nuclei
RED: Hpa-1 BLUE:Nuclei
Hypothesis
Hspe-1 expression during limb
development facilitates delivery of
HBGFs (i.e. FGFs, BMPs, Ihh) that
regulate tissue growth and
maturation.
Sample of long bones microdissected
from mouse toes
Percent of
Growth
D0
D5
14%
#1
2.827
3.227
23%
#2
2.733
3.373
17%
#3
2.240
2.613
16%
#4
2.827
Mean 17.5 +/- 3.9
3.293
The effects of a heparanase inhibitor
on long bone growth
% Growth
40
30
20
10
0
0
100
Concentration of PI88 (ug/ml)
Heparanase Inhibitor
So what do I study and why
should you care…
I study the role of heparanase in bone
growth.
My research will provide information for
tissue engineers when determining the
necessary molecules to coat biodegradable
scaffolds to assist with tissue regeneration
during bone fractures and degradation.