Clinical plasma concentration of vinpocetine does not affect osteogenic differentiation of mesenchymal stem cells
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ARTICLE
Clinical plasma concentration of vinpocetine does not affect osteogenic differentiation of mesenchymal stem cells Esma Yıldırım1 · Gulay Sezer2,3 Received: 12 May 2020 / Revised: 17 July 2020 / Accepted: 20 August 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
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. Keywords Vinpocetine · Mesenchymal stem cells · Osteogenic differentation · NF-kappa B · Runx2 · ALP 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 * Gulay Sezer [email protected] 1
Pharmacy Division, Ministry of Health Kayseri City Hospital, 38080 Kayseri, Turkey
2
School of Medicine, Pharmacology Department, Erciyes University, 38039 Kayseri, Turkey
3
Genkok Genome and Stem Cell Centre, Erciyes University, Kayseri, Turkey
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
Introduction Osteoporosis and cerebrovascular disorders are common diseases in the elderly population. Studies have revealed that many elderly patients with osteoporosis are associated with cerebral infarction [1]. Additionally, stroke is frequently followed
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