Heparanase (Hpa1) Expression and its Function

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

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

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

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

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.

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

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 17.5 +/- 3.9

The effects of a heparanase inhibitor on long bone growth

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.