Heparanase (Hpa1) Expression and its Function in Bone Development

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.