1. Heparanase (Hpa1) Expression and its Function
in Bone Development
Dr. Cindy Farach-Carson
Dr. Daniel Carson

2. Cells Tissues Organs How does this relate to my “science project”?
Factor A C B
How does this relate to my “science project”?

3. (HSPG) [Sugar Protein]
Heparan Sulfate
Proteoglycan
(HSPG) [Sugar Protein]
Heparanase
(an enzyme)
Growth
Factor and
Receptor
Molecule for
cleavage
Organs
Cells
Tissues
Cartilage/Bone

4. What molecules are important for bone development and growth?
a trimolecular complex Hz
PHz Pz
Formation of trimolecular complex confers resistance on the gfs to proteolysis and thermal denaturation and provides a reservoir of growth and migration factors that can be mobilized in accordance with physiological demand
Image modified from Miller et al., Differentiation (2003) 71:1-15
PZ = proliferative zone PHz= Prehypertrophic Zone
Hz= Hypertrophic Zone

5. RED: Perlecan GREEN: Hpa-1
Heparanase-1 (Hpa-1), a member of the trimolecular complex, expression in mouse limb and chondrocytes
In vivo
In vitro
RED: Perlecan GREEN: Hpa-1
BLUE:Nuclei
PHz Hz Pc MT B.
RED: Hpa-1 BLUE:Nuclei A.

6. Hypothesis Hspe-1 expression during limb
development facilitates delivery of
HBGFs (i.e. FGFs, BMPs, Ihh) that
regulate tissue growth and
maturation.
HBGFs = FGF which is essential for the diff. of mesenchymal cells into chondrocytes

8. Sample of long bones microdissected from mouse toes#1 #2 #3 #4
2.827
3.227
2.733
2.240
3.373
2.613
3.293
14%
Percent of
Growth
23%
17%
16%
Mean /- 3.9

9. The effects of a heparanase inhibitor on long bone growth

10. 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.