Abstract
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.
Highlights
Angiogenesis, the formation of new blood vessels from existing ones, is indispensable for bone regeneration and maintenance of bone health [1,2,3]
We demonstrate that expression and protein levels of the angiogenic mediator molecules Vascular endothelial growth factor (VEGF), stromal-derived factor 1 (SDF-1), ANG-1 were downregulated in the Mesenchymal stem cells (MSC) mono-culture and Angiopoietin 2 (ANG-2) was downregulated in the outgrowth endothelial cells (OEC) mono-culture
To reveal more details on how fucoidans interfere with the angiogenic process on a molecular level, we determined expression and protein level of the angiogenic mediators VEGF, ANG-1, ANG-2 and SDF-1 in OEC-MSC co-culture after 7 days of treatment
Summary
Angiogenesis, the formation of new blood vessels from existing ones, is indispensable for bone regeneration and maintenance of bone health [1,2,3]. To better understand how fucoidans affect angio- and osteogenic processes on a molecular level in a bone tissue setting and what influence chemical properties have, we treated mono- and co-cultures of primary endothelial and osteoblast-like cells with four chemically well-characterized fucoidan extracts and quantified expression and protein levels of the important angiogenic regulators VEGF, SDF-1, ANG-1 and ANG-2. This paper (a) describes the bioactivity of four chemically well-characterized fucoidan extracts on angio- and osteogenesis in a mono- and co-culture system mimicking bone tissue, (b) provides information about the relationship between reported activities and chemical properties of the extracts, and (c) discusses a possible mechanism of action of HMW fucoidans in the context of angiogenesis in the mono- and co-culture systems
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
