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. Electronic supplementary material The online version of this article (10.1186/s12929-019-0544-7) contains supplementary material, which is available to authorized users.

Effective Inhibition of Candidiasis Using an Eco-Friendly Leaf Extract of Calotropis-gigantean-Mediated Silver Nanoparticles

“…The cells were seeded in 96-well plates and treated with different concentrations of either AgNPs or AgNPs/CG for 48 h. The cells were then washed with PBS and incubated with fresh medium containing 0.5 mg/mL MTT to metabolize to formazan. The optical density was determined at 550 nm using an ELISA plate reader [37]. Cell viability was represented as a percentage of the control non-treated cells.…”

The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

“…5′-HA was extracted from Lotus lalambensis Schweinf (collected from Saudi Arabia). e extraction and identification of 5′-HA were performed as described previously by our group [20].…”

“…Furthermore, psoralidin, osthole, and aesculin were protective against bone loss in osteoporotic mouse models [17][18][19]. Recently, we identified a coumarin derivative, 5′-HA ([7-(5-hydroxy-3,7-dimethylocta-2,6-dienyloxy)-chromen-2-one]), as a novel compound that functions to stimulate osteoblast differentiation from BM-derived stromal stem cells in BMPdependent mechanism [20]. To provide more detailed information on the effect of 5′-HA on bone metabolism, we aimed in this study to investigate the effect of 5′-HA on osteoclast differentiation of murine BM cells as well as to elucidate its molecular mechanism.…”

A Review of the Pharmacological Properties of Psoralen

“…BMP-2/4 promote the expression of ALP and Col-I ( Soundharrajan et al, 2018 ) and bind to the cell surface receptors on bone cells, inducing the phosphorylation of Smad1/5/8. Subsequently, Smad4 combines with phosphorylated Smad1/5/8 and is transported to the nucleus where it activates bone-specific gene transcription, and accordingly stimulates bone formation ( Abdallah and Ali, 2019 ; Jungbluth et al, 2019 ). It has been further established that psoralen enhances the gene expression levels of BMP-2/4, increases phospho-Smad1/5/8 protein expression and induces the activity of BMP reporter 12xSBE-OC-Luc.…”