5'-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism

Basem M Abdallah, Enas M Ali

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Abstract

BACKGROUND: Identifying bone anabolic agents is a superior strategy for the treatment of osteoporosis. Naturally, derived coumarin derivatives have shown osteoanabolic effect in vitro and in vivo. In this study, we investigated the effect of 5'-Hydroxy Auraptene (5'-HA), a coumarin derivative that newly isolated from Lotus lalambensis Schweinf on the differentiation of the mouse bone marrow-derived mesenchymal (skeletal) stem cells (mBMSCs) into osteoblast and adipocyte.

METHODS: The effect of 5'-HA on mBMSCs cell proliferation and osteoblast differentiation was assessed by measuring cell viability, quantitative alkaline phosphatase (ALP) activity assay, Alizarin red staining for matrix mineralization and osteogenic gene array expression. Adipogenesis was measured by Oil Red O staining and quantitative real time PCR (qPCR) analysis of adipogenic markers. Regulation of BMPs signaling pathways by 5'-HA was measured by Western blot analysis and qPCR.

RESULTS: 5'-HA showed to stimulate the differentiation of mBMSCs into osteogenic cell lineage in a dose-dependent manner, without affecting their differentiation into adipocytic cell lineage. Treatment of mBMSCs with 5'-HA showed to promote significantly the BMP2-induced osteogenesis in mBMSCs via activating Smad1/5/8 phosphorylation and increasing Smad4 expression. Blocking of BMP signaling using BMPR1 selective inhibitor LDN-193189 significantly inhibited the stimulatory effect of 5'-HA on osteogenesis.

CONCLUSIONS: Our data identified 5'-HA, as a novel coumarin derivative that function to stimulate the differentiation of mBMSCs into osteoblasts in BMP-signaling dependent mechanism.

Original languageEnglish
Article number51
JournalJournal of Biomedical Science
Volume26
Number of pages11
ISSN1021-7770
DOIs
Publication statusPublished - 5. Jul 2019

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Osteoblasts
Stem cells
Mesenchymal Stromal Cells
Bone
Coumarins
Cell Lineage
Osteogenesis
Anabolic Agents
Adipogenesis
Phosphorylation
Cell proliferation
aurapten
Adipocytes
Alkaline Phosphatase
Real-Time Polymerase Chain Reaction
Assays
Cell Survival
Genes
Cells
Cell Proliferation

Keywords

  • 5-hydroxy aurapten
  • Adipocyte
  • BMSCs
  • Mesenchymal stem cells
  • Osteoblast
  • Osteoblast differentiation

Cite this

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title = "5'-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism",
abstract = "BACKGROUND: Identifying bone anabolic agents is a superior strategy for the treatment of osteoporosis. Naturally, derived coumarin derivatives have shown osteoanabolic effect in vitro and in vivo. In this study, we investigated the effect of 5'-Hydroxy Auraptene (5'-HA), a coumarin derivative that newly isolated from Lotus lalambensis Schweinf on the differentiation of the mouse bone marrow-derived mesenchymal (skeletal) stem cells (mBMSCs) into osteoblast and adipocyte.METHODS: The effect of 5'-HA on mBMSCs cell proliferation and osteoblast differentiation was assessed by measuring cell viability, quantitative alkaline phosphatase (ALP) activity assay, Alizarin red staining for matrix mineralization and osteogenic gene array expression. Adipogenesis was measured by Oil Red O staining and quantitative real time PCR (qPCR) analysis of adipogenic markers. Regulation of BMPs signaling pathways by 5'-HA was measured by Western blot analysis and qPCR.RESULTS: 5'-HA showed to stimulate the differentiation of mBMSCs into osteogenic cell lineage in a dose-dependent manner, without affecting their differentiation into adipocytic cell lineage. Treatment of mBMSCs with 5'-HA showed to promote significantly the BMP2-induced osteogenesis in mBMSCs via activating Smad1/5/8 phosphorylation and increasing Smad4 expression. Blocking of BMP signaling using BMPR1 selective inhibitor LDN-193189 significantly inhibited the stimulatory effect of 5'-HA on osteogenesis.CONCLUSIONS: Our data identified 5'-HA, as a novel coumarin derivative that function to stimulate the differentiation of mBMSCs into osteoblasts in BMP-signaling dependent mechanism.",
keywords = "5-hydroxy aurapten, Adipocyte, BMSCs, Mesenchymal stem cells, Osteoblast, Osteoblast differentiation",
author = "Abdallah, {Basem M} and Ali, {Enas M}",
year = "2019",
month = "7",
day = "5",
doi = "10.1186/s12929-019-0544-7",
language = "English",
volume = "26",
journal = "Journal of Biomedical Science",
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5'-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism. / Abdallah, Basem M; Ali, Enas M.

In: Journal of Biomedical Science, Vol. 26, 51, 05.07.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - 5'-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism

AU - Abdallah, Basem M

AU - Ali, Enas M

PY - 2019/7/5

Y1 - 2019/7/5

N2 - BACKGROUND: Identifying bone anabolic agents is a superior strategy for the treatment of osteoporosis. Naturally, derived coumarin derivatives have shown osteoanabolic effect in vitro and in vivo. In this study, we investigated the effect of 5'-Hydroxy Auraptene (5'-HA), a coumarin derivative that newly isolated from Lotus lalambensis Schweinf on the differentiation of the mouse bone marrow-derived mesenchymal (skeletal) stem cells (mBMSCs) into osteoblast and adipocyte.METHODS: The effect of 5'-HA on mBMSCs cell proliferation and osteoblast differentiation was assessed by measuring cell viability, quantitative alkaline phosphatase (ALP) activity assay, Alizarin red staining for matrix mineralization and osteogenic gene array expression. Adipogenesis was measured by Oil Red O staining and quantitative real time PCR (qPCR) analysis of adipogenic markers. Regulation of BMPs signaling pathways by 5'-HA was measured by Western blot analysis and qPCR.RESULTS: 5'-HA showed to stimulate the differentiation of mBMSCs into osteogenic cell lineage in a dose-dependent manner, without affecting their differentiation into adipocytic cell lineage. Treatment of mBMSCs with 5'-HA showed to promote significantly the BMP2-induced osteogenesis in mBMSCs via activating Smad1/5/8 phosphorylation and increasing Smad4 expression. Blocking of BMP signaling using BMPR1 selective inhibitor LDN-193189 significantly inhibited the stimulatory effect of 5'-HA on osteogenesis.CONCLUSIONS: Our data identified 5'-HA, as a novel coumarin derivative that function to stimulate the differentiation of mBMSCs into osteoblasts in BMP-signaling dependent mechanism.

AB - BACKGROUND: Identifying bone anabolic agents is a superior strategy for the treatment of osteoporosis. Naturally, derived coumarin derivatives have shown osteoanabolic effect in vitro and in vivo. In this study, we investigated the effect of 5'-Hydroxy Auraptene (5'-HA), a coumarin derivative that newly isolated from Lotus lalambensis Schweinf on the differentiation of the mouse bone marrow-derived mesenchymal (skeletal) stem cells (mBMSCs) into osteoblast and adipocyte.METHODS: The effect of 5'-HA on mBMSCs cell proliferation and osteoblast differentiation was assessed by measuring cell viability, quantitative alkaline phosphatase (ALP) activity assay, Alizarin red staining for matrix mineralization and osteogenic gene array expression. Adipogenesis was measured by Oil Red O staining and quantitative real time PCR (qPCR) analysis of adipogenic markers. Regulation of BMPs signaling pathways by 5'-HA was measured by Western blot analysis and qPCR.RESULTS: 5'-HA showed to stimulate the differentiation of mBMSCs into osteogenic cell lineage in a dose-dependent manner, without affecting their differentiation into adipocytic cell lineage. Treatment of mBMSCs with 5'-HA showed to promote significantly the BMP2-induced osteogenesis in mBMSCs via activating Smad1/5/8 phosphorylation and increasing Smad4 expression. Blocking of BMP signaling using BMPR1 selective inhibitor LDN-193189 significantly inhibited the stimulatory effect of 5'-HA on osteogenesis.CONCLUSIONS: Our data identified 5'-HA, as a novel coumarin derivative that function to stimulate the differentiation of mBMSCs into osteoblasts in BMP-signaling dependent mechanism.

KW - 5-hydroxy aurapten

KW - Adipocyte

KW - BMSCs

KW - Mesenchymal stem cells

KW - Osteoblast

KW - Osteoblast differentiation

U2 - 10.1186/s12929-019-0544-7

DO - 10.1186/s12929-019-0544-7

M3 - Journal article

VL - 26

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

M1 - 51

ER -