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

  • Matthew Allen Carson

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

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 in vitro 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.
A small subset of promising extracts were subsequently tested in vivo, 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 Ceramium secundatum, Ceramium pallidum and Plocamium lyngbyanum showing excellent effects. Taking P. lyngbyanum 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.
Date of AwardMar 2018
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorSusan Clarke (Supervisor), John Nelson (Supervisor) & Brendan Gilmore (Supervisor)

Keywords

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

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