Discovering bioactive compounds for bone growth: the osteogenicity of marine organism-derived extracts

Through the current trend for bioprospecting, marine organisms - particularly algae - are becoming increasingly known for their osteogenic potential. Such organisms may provide novel treatment options for osteoporosis and other musculoskeletal conditions, helping to address their large healthcare burden and the limitations of current therapies. This study focused on screening for marine-organism derived osteogenic (promoting bone formation) activity, using extracts produced from a wide range of taxonomic groups sourced from the west coast of Ireland. In total, 100+ extracts were screened <i>in vitro</i> for their osteogenic potential, using both a human foetal osteoblast (hFOB) cell line and human bone marrow derived stromal cells (hBMSCs - primary cells). Extracts were tested for cytotoxicity, as well as their effects on cell proliferation and differentiation, both through changes in alkaline phosphatase expression and eventual mineralisation levels.<br/>A small subset of promising extracts were subsequently tested <i>in vivo</i>, using two zebrafish models; one investigating operculum bone growth in juveniles and the other caudal fin regeneration in adults. The operculum system was particularly effective, showing a large number of extracts to significantly increase the degree of bone growth relative to control. Of those extracts tested, red algae were particularly active, with species such as <i>Ceramium secundatum</i>, <i>Ceramium pallidum</i> and <i>Plocamium lyngbyanum</i> showing excellent effects. Taking <i>P. lyngbyanum</i> as an example, increases compared to control of approximately 120% were seen for hBMSC proliferation, +100% for differentiation, +200% for mineralisation and +60% for zebrafish operculum bone growth. If also active in humans, these extracts could help to promote bone growth in those suffering from conditions such as osteoporosis; allowing increases in bone mineral density, a better quality of life and reduced costs for NHS services. Future work should focus on elucidating the exact bioactive component of each extract and its mechanism of effect.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2018

Author dc:creator

• Carson, Matthew Allen

Advisors dc:contributor.advisor

• Clarke, Susan
• Gilmore, Brendan

• bioactivity screening
• osteogenic compounds
• marine extract
• zebrafish
• Danio rerio
• mesenchymal stem cells
• red algae
• matrix mineralisation
• Ceramium pallidum
• Ceramium secundatum
• Plocamium cartilagineum

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/ef67d00c-f0da-440d-95a3-bf7b840a8b1f

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/ef67d00c-f0da-440d-95a3-bf7b840a8b1f