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Clinical plasma concentration of vinpocetine does not affect osteogenic differentiation of mesenchymal stem cells

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Abstract

Aim

Vinpocetine (Vin) has long been used as a medicine to treat cerebrovascular disorders and as a dietary supplement to improve cognitive functions. Previous studies have revealed that the transcription factor nuclear factor kappa B (NF-κB) activity plays an important role in osteogenic differentiation of mesenchymal stem cells (MSC). Vin inhibits NF-κB-dependent inflammatory responses; however, the effect of Vin on the osteogenic differentiation of MSCs has not been reported. In this study, we aimed to the investigate effect of Vin on the osteogenic differentiation of rat bone marrow-derived MSCs (BMSCs).

Methods

We treated BMSCs with clinical plasma (0.17 µM) or higher concentrations (5 and 20 µM) of Vin with no significant effect on the cell viability. Alizarin Red S and alkaline phosphatase (ALP) stainings were used to evaluate mineralizations on days 14 and 21. Moreover, expressions of target genes were detected using qRT-PCR analysis.

Results

Osteogenic differentiation of BMSCs did not significantly change with Vin’s clinical plasma concentration, but significantly decreased with higher concentrations. Calcium mineralization, ALP staining and mRNA gene expressions of Runx2 and ALP were decreased significantly with high concentrations of Vin, paticularly on day 21.

Conclusion

Our in vitro findings suggest that clinically relevant concentration of Vin seems safe to use in elderly patients with respect to osteoporosis. On the other hand, Vin at high concentrations appears to be harmful to bone homeostasis.

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Abbreviations

ALP:

Alkaline phosphatase

BMSCs:

Bone marrow-derived mesenchymal stem cells

BMP-4:

Bone morphogenetic protein 4

ColIa1:

Collagen type I alpha 1

DMSO:

Dimethyl sulfoxide

DMEM-LG:

Dulbecco’s modified Eagle’s medium-low sugar

DPBS:

Dulbecco’s phosphate-buffered saline

FBS:

Fetal bovine serum

IKK:

IκB kinase

IKKβ:

IκB kinase β

MSCs:

Mesenchymal stem cells

NF-κB:

Nuclear factor kappa B

ODM:

Osteogenic differentiation medium

PDE 1:

Phosphodiesterase type 1

Runx2:

Runt-related transcription factor 2

VSMCs:

Vascular smooth muscle cells

Vin:

Vinpocetine

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Funding

This work was supported by the Scientific Research Projects Coordination Unit of Erciyes University (project code: TYL-2018-8300).

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Authors and Affiliations

  1. Pharmacy Division, Ministry of Health Kayseri City Hospital, 38080, Kayseri, Turkey

    Esma Yıldırım

  2. School of Medicine, Pharmacology Department, Erciyes University, 38039, Kayseri, Turkey

    Gulay Sezer

  3. Genkok Genome and Stem Cell Centre, Erciyes University, Kayseri, Turkey

    Gulay Sezer

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  1. Esma Yıldırım
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  2. Gulay Sezer
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Both authors participated in the study design, in vitro experiments, interpretation, data analysis, and review of the manuscript. GS contributed to writing and editing of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gulay Sezer.

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Yıldırım, E., Sezer, G. Clinical plasma concentration of vinpocetine does not affect osteogenic differentiation of mesenchymal stem cells. Pharmacol. Rep 73, 202–210 (2021). https://doi.org/10.1007/s43440-020-00153-8

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  • DOI: https://doi.org/10.1007/s43440-020-00153-8

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