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Heparanase (Hpa1) Expression and its Function Heparanase (Hpa1) Expression and its Function in Bone Development in Bone Development Dr. Cindy Farach-Carson Dr. Daniel Carson
Heparanase (Hpa1) Expression and its Function Heparanase (Hpa1) Expression and its Function in Bone Developmentin Bone Development
Dr. Cindy Farach-Carson Dr. Daniel Carson
OrgansOrgans
CellsCells
TissuesTissues
Factor A
Factor C
Factor B
How does this relate to my “science project”?How does this relate to my “science project”?
OrgansOrgans
CellsCells
TissuesTissues
Growth Factor andReceptor
Heparan SulfateProteoglycan
(HSPG) [Sugar Protein]
HeparanaseHeparanase(an enzyme)(an enzyme)
Cartilage/BoneCartilage/Bone
Molecule for cleavage
What molecules are important for bone development and growth?
Hz
PHz
Pz
Image modified from Miller et al., Differentiation (2003) 71:1-15
PZ = proliferative zone PHz= Prehypertrophic Zone Hz= Hypertrophic Zone
a trimolecular complexa trimolecular complex
Heparanase-1 (Hpa-1), a member of the trimolecular complex, expression in
mouse limb and chondrocytes
RED: Perlecan GREEN: Hpa-1 BLUE:Nuclei
PHz
Hz
Pc
MT
B.
RED: Hpa-1 BLUE:Nuclei
A.
In vivo In vitro
Hypothesis
Hspe-1 expression during limb development facilitates delivery of HBGFs (i.e. FGFs, BMPs, Ihh) that regulate tissue growth and maturation.
D0 D5
#1
#2
#3
#4
2.827 3.227
2.733
2.240
2.827
3.373
2.613
3.293
14%
Percent of Growth
23%
17%
16%
Mean 17.5 +/- 3.9
Sample of long bones microdissected from mouse toes
0 1000
10
20
30
40
Concentration of PI88 (ug/ml)
% G
row
th
The effects of a heparanase inhibitor on long bone growth
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.
