gms | German Medical Science

Angiogenesis, the formation of blood vessels from existing ones, is a prerequisite for the regeneration of bone defects. But out of balance, angiogenesis is also associated with severe bone-related diseases like arthritis or osteosarcoma. Fucoidans, sulfated polysaccharides from brown algae, have raised great interest in the scientific and medical community because of its numerous reported biological activities, including effects on angiogenesis. The chemical heterogeneity however, complicates the development of fucoidan-based therapies. Important structural properties like monosaccharide content, degree of sulfation and molecular weight, likely determining fucoidans’ bioactivities, depend on species, time of harvesting and extraction technique. The use of different and only partially characterized fucoidans make studies hard to compare and a clear structure-bioactivity relationship hard to define. In this study, we investigated the effect of four chemically well-characterized fucoidans on angiogenesis and osteogenesis in bone-related mono- and co-culture systems. Crude fucoidan was enzymatically extracted from Fucus evanescens and purified into three fractions using ion-exchange chromatography. Monosaccharide content, degree of sulfation and molecular weight were determined for each extract. Outgrowth endothelial cells (OEC) and mesenchymal stem cells, differentiated to osteoblast-like cells (MSC), were treated with the fucoidan extracts for seven days. After determining the potential toxicity and appropriate doses of the extracts, mono- and co-culture systems were applied to study the effect of fucoidan on important angiogenic and osteogenic markers and regulatory molecules. We show that fucoidan treatment reduces the expression and protein production of vascular endothelial growth factor (VEGF), stromal-derived factor 1 (SDF-1), angiopoietin-1 and -2 (ANG-1, ANG-2) and alkaline phosphatase (ALP) in the mono-culture systems. Immunocytochemistry revealed a reduction of angiogenic tube-like structures in OEC-MSC co-cultures that were treated with the fucoidan fractions. Despite an impaired formation of angiogenic tube-like structures, VEGF protein levels were increased in co-culture systems that were treated with fucoidan. We find that purer fucose- and sulfate-rich fucoidans negatively influence angiogenic and osteogenic processes stronger. Our study emphasizes how structural properties influence the bioactivity of fucoidans in a bone-related context and thus gives valuable information for the development of fucoidan-containing therapies. Depending on pro- or anti-angiogenic effects, fucoidans can be applied systematically in tissue engineering approaches assisting the regeneration of bone defects or in therapeutic applications treating bone-related diseases like osteosarcoma.