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Open AccessArticle

Effect of Enzymatically Extracted Fucoidans on Angiogenesis and Osteogenesis in Primary Cell Culture Systems Mimicking Bone Tissue Environment

1
Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany
2
Protein Chemistry and Enzyme Technology Section, DTU Bioengineering, Department of Biotechnology and Biomedicine, Technical University of Denmark, Building 221, 2800 Kongens Lyngby, Denmark
3
MetaPhysiol, Am Römerberg, 55270 Essenheim, Germany
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(9), 481; https://doi.org/10.3390/md18090481
Received: 24 July 2020 / Revised: 2 September 2020 / Accepted: 18 September 2020 / Published: 21 September 2020
(This article belongs to the Special Issue Marine Organisms for Bone Regeneration - 2020)
Angiogenesis, the formation of new blood vessels from existing ones, is an essential process for successful bone regeneration. Further, angiogenesis is a key factor for the development of bone-related disorders like osteosarcoma or arthritis. Fucoidans, sulfated polysaccharides from brown algae, have been shown to affect angiogenesis as well as a series of other physiological processes including inflammation or infection. However, the chemical properties of fucoidan which define the biological activity vary tremendously, making a prediction of the bioactivity or the corresponding therapeutic effect difficult. In this study, we compare the effect of four chemically characterized high molecular weight fucoidan extracts from Fucus distichus subsp. evanescens (FE_crude and fractions F1, F2, F3) on angiogenic and osteogenic processes in bone-related primary mono- and co-culture cell systems. By determining the gene expression and protein levels of the regulatory molecules vascular endothelial growth factor (VEGF), angiopoietin-1 (ANG-1), ANG-2 and stromal-derived factor 1 (SDF-1), we show that the extracted fucoidans negatively influence angiogenic and osteogenic processes in both the mono- and co-culture systems. We demonstrate that purer fucoidan extracts with a high fucose and sulfate content show stronger effects on these processes. Immunocytochemistry of the co-culture system revealed that treatment with FE_F3, containing the highest fucose and sulfate content, impaired the formation of angiogenic tube-like structures, indicating the anti-angiogenic properties of the tested fucoidans. This study highlights how chemical properties of fucoidan influence its bioactivity in a bone-related context and discusses how the observed phenotypes can be explained on a molecular level—knowledge that is indispensable for future therapies based on fucoidans. View Full-Text
Keywords: fucoidan; angiogenesis; osteogenesis; Fucus evanescens; outgrowth endothelial cells; mesenchymal stem cells; VEGF; angiopoietin; enzyme-assisted extraction; sulfation degree fucoidan; angiogenesis; osteogenesis; Fucus evanescens; outgrowth endothelial cells; mesenchymal stem cells; VEGF; angiopoietin; enzyme-assisted extraction; sulfation degree
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Ohmes, J.; Xiao, Y.; Wang, F.; Mikkelsen, M.D.; Nguyen, T.T.; Schmidt, H.; Seekamp, A.; Meyer, A.S.; Fuchs, S. Effect of Enzymatically Extracted Fucoidans on Angiogenesis and Osteogenesis in Primary Cell Culture Systems Mimicking Bone Tissue Environment. Mar. Drugs 2020, 18, 481.

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