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Open AccessArticle

Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts

1
Department of Materials Science and Engineering, INSIGNEO Institute for in silico medicine, The Pam Liversidge Building, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, UK
2
Department of Materials Science and Engineering, University of Sheffield, Kroto Research Institute, Sheffield S3 7HQ, UK
3
Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
*
Author to whom correspondence should be addressed.
Co-first authors.
Bioengineering 2020, 7(1), 12; https://doi.org/10.3390/bioengineering7010012
Received: 29 November 2019 / Revised: 13 January 2020 / Accepted: 15 January 2020 / Published: 21 January 2020
(This article belongs to the Special Issue Assessments and Advances in Bone Regeneration, Therapies and Healing)
There is variability in the reported effects of compounds on osteoblasts arising from differences in experimental design and choice of cell type/origin. This makes it difficult to discern a compound’s action outside its original study and compare efficacy between compounds. Here, we investigated five compounds frequently reported as anabolic for osteoblasts (17β-estradiol (oestrogen), icariin, lactoferrin, lithium chloride, and menaquinone-4 (MK-4)) on human mesenchymal progenitors to assess their potential for bone tissue engineering with the aim of identifying a potential alternative to expensive recombinant growth factors such as bone morphogenetic protein 2 (BMP-2). Experiments were performed using the same culture conditions to allow direct comparison. The concentrations of compounds spanned two orders of magnitude to encompass the reported efficacious range and were applied continuously for 22 days. The effects on the proliferation (resazurin reduction and DNA quantification), osteogenic differentiation (alkaline phosphatase (ALP) activity), and mineralised matrix deposition (calcium and collagen quantification) were assessed. Of these compounds, only 10 µM MK-4 stimulated a significant anabolic response with 50% greater calcium deposition. Oestrogen and icariin had no significant effects, with the exception of 1 µM icariin, which increased the metabolic activity on days 8 and 22. 1000 µg/mL of lactoferrin and 10 mM lithium chloride both significantly reduced the mineralised matrix deposition in comparison to the vehicle control, despite the ALP activity being higher in lithium chloride-treated cells at day 15. This demonstrates that MK-4 is the most powerful stimulant of bone formation in hES-MPs of the compounds investigated, highlighting its potential in bone tissue engineering as a method of promoting bone formation, as well as its prospective use as an osteoporosis treatment.
Keywords: matrix mineralisation; osteoblasts; bone formation; mesenchymal stem cells; osteoporosis; bone tissue engineering; menaquinone-4; vitamin K matrix mineralisation; osteoblasts; bone formation; mesenchymal stem cells; osteoporosis; bone tissue engineering; menaquinone-4; vitamin K
MDPI and ACS Style

Owen, R.; Bahmaee, H.; Claeyssens, F.; Reilly, G.C. Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts. Bioengineering 2020, 7, 12.

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