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

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 invest...

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Main Authors: Robert Owen, Hossein Bahmaee, Frederik Claeyssens, Gwendolen C. Reilly
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Bioengineering
Subjects:
Online Access:https://www.mdpi.com/2306-5354/7/1/12
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author Robert Owen
Hossein Bahmaee
Frederik Claeyssens
Gwendolen C. Reilly
author_facet Robert Owen
Hossein Bahmaee
Frederik Claeyssens
Gwendolen C. Reilly
author_sort Robert Owen
collection DOAJ
description 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.
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spelling doaj.art-134222c2a7f64e0097c1d4cb3fe7dcea2023-08-02T00:45:41ZengMDPI AGBioengineering2306-53542020-01-01711210.3390/bioengineering7010012bioengineering7010012Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived OsteoblastsRobert Owen0Hossein Bahmaee1Frederik Claeyssens2Gwendolen C. Reilly3Department of Materials Science and Engineering, INSIGNEO Institute for in silico medicine, The Pam Liversidge Building, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, UKDepartment of Materials Science and Engineering, INSIGNEO Institute for in silico medicine, The Pam Liversidge Building, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, UKDepartment of Materials Science and Engineering, INSIGNEO Institute for in silico medicine, The Pam Liversidge Building, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, UKDepartment of Materials Science and Engineering, INSIGNEO Institute for in silico medicine, The Pam Liversidge Building, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, UKThere 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.https://www.mdpi.com/2306-5354/7/1/12matrix mineralisationosteoblastsbone formationmesenchymal stem cellsosteoporosisbone tissue engineeringmenaquinone-4vitamin k
spellingShingle Robert Owen
Hossein Bahmaee
Frederik Claeyssens
Gwendolen C. Reilly
Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts
Bioengineering
matrix mineralisation
osteoblasts
bone formation
mesenchymal stem cells
osteoporosis
bone tissue engineering
menaquinone-4
vitamin k
title Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts
title_full Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts
title_fullStr Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts
title_full_unstemmed Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts
title_short Comparison of the Anabolic Effects of Reported Osteogenic Compounds on Human Mesenchymal Progenitor-derived Osteoblasts
title_sort comparison of the anabolic effects of reported osteogenic compounds on human mesenchymal progenitor derived osteoblasts
topic matrix mineralisation
osteoblasts
bone formation
mesenchymal stem cells
osteoporosis
bone tissue engineering
menaquinone-4
vitamin k
url https://www.mdpi.com/2306-5354/7/1/12
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AT frederikclaeyssens comparisonoftheanaboliceffectsofreportedosteogeniccompoundsonhumanmesenchymalprogenitorderivedosteoblasts
AT gwendolencreilly comparisonoftheanaboliceffectsofreportedosteogeniccompoundsonhumanmesenchymalprogenitorderivedosteoblasts