The use of heparan sulfate to augment fracture repair in a rat fracture model.
Fracture healing is a complex process regulated by numerous growth and adhesive factors expressed at specific stages during healing. The naturally occurring, cell surface-expressed sugar, heparan sulfate (HS), is known to bind to and potentiate the effects of many classes of growth factors, and as such, may be a potential candidate therapy for enhancing bone repair. This study investigated the local application of bone-derived HS in the repair of rat femoral fractures. After 2 weeks, there was a significant increase in the callus size of rats administered with 5 microg HS compared to the control and 50 microg HS groups, presumably due to increased trabecular bone volume rather than increased cartilage production. In addition, 5 microg HS increased the expression of ALP, Runx2, FGF-1, IGF-II, TGF-beta1, and VEGF. It is hypothesized that these increases resulted from changes in HS-mediated receptor/ligand interactions that increase local growth factor production to augment bone formation. The findings of this study demonstrate the anabolic potential of HS in bone repair by recruiting and enhancing the production of endogenous growth factors at the site of injury.
Jackson
Rebecca A
RA
School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland, 4072 Australia.
McDonald
Michelle M
MM
Nurcombe
Victor
V
Little
David G
DG
Cool
Simon M
SM
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D015519:Bone Density; D017102:Fracture Healing / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006497:Heparan Sulfate / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000469:Alkaline Phosphatase; D006497:Heparan Sulfate; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C508962:Tgfb1 protein, rat