University of Oulu

Uzieliene I, Bernotiene E, Rakauskiene G, Denkovskij J, Bagdonas E, Mackiewicz Z, Porvaneckas N, Kvederas G and Mobasheri A (2019) The Antihypertensive Drug Nifedipine Modulates the Metabolism of Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells. Front. Endocrinol. 10:756. doi: 10.3389/fendo.2019.00756

The antihypertensive drug nifedipine modulates the metabolism of chondrocytes and human bone marrow-derived mesenchymal stem cells

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Author: Uzieliene, Ilona1; Bernotiene, Eiva1; Rakauskiene, Greta1;
Organizations: 1Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
2Faculty of Medicine, Vilnius University, Vilnius, Lithuania
3Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
4Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, Queen's Medical Centre, Nottingham, United Kingdom
5Sheik Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis With Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202002185661
Language: English
Published: Frontiers Media, 2019
Publish Date: 2020-02-18
Description:

Abstract

Aging is associated with the development of various chronic diseases, in which both cardiovascular disorders and osteoarthritis are dominant. Currently, there is no effective treatment for osteoarthritis, whereas hypertension is often treated with L-type voltage-operated calcium channel blocking drugs, nifedipine being among the most classical ones. Although nifedipine together with other L-type voltage-operated calcium channel inhibitors plays an important role in controlling hypertension, there are unresolved questions concerning its possible effect on cartilage tissue homeostasis and the development of osteoarthritis. The aim of this study was to analyse the effects of nifedipine on metabolic processes in human chondrocytes and bone marrow mesenchymal stem cells. To better understand whether the metabolic effects are mediated specifically through L-type voltage-operated calcium channel, effects of the agonist BayK8644 were analyzed in parallel. Nifedipine downregulated and mitochondrial respiration and ATP production in both cell types. Analysis of cartilage explants by electron microscopy also suggested that a small number of chondrocyte mitochondria's lose their activity in response to nifedipine. Conversely, nifedipine enhanced glycolytic capacity in chondrocytes, suggesting that these cells have the capacity to switch from oxidative phosphorylation to glycolysis and alter their metabolic activity in response to L-type voltage-operated calcium channel inhibition. Such a metabolic switch was not observed in bone marrow mesenchymal stem cells. Nitric oxide activity was upregulated by nifedipine in bone marrow mesenchymal stem cells and particularly in chondrocytes, implying its involvement in the effects of nifedipine on metabolism in both tested cell types. Furthermore, stimulation with nifedipine resulted in elevated production of collagen type II and glycosaminoglycans in micromass cultures under chondrogenic conditions. Taken together, we conclude that the antihypertensive drug nifedipine inhibits mitochondrial respiration in both chondrocytes and bone marrow mesenchymal stem cells and that these effects may be associated with the increased nitric oxide accumulation and pro-inflammatory activity. Nifedipine had positive effects on the production of collagen type II and proteoglycans in both cell types, implying potentially beneficial anabolic responses in articular cartilage. These results highlight a potential link between antihypertensive drugs and cartilage health.

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Series: Frontiers in endocrinology
ISSN: 1664-2392
ISSN-E: 1664-2392
ISSN-L: 1664-2392
Volume: 10
Article number: 756
DOI: 10.3389/fendo.2019.00756
OADOI: https://oadoi.org/10.3389/fendo.2019.00756
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: This work was funded by the European Social Fund according to the activity Improvement of researchers' qualification by implementing world-class R&D projects' of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215). The research underpinning the work presented has received funding from a number of sources including: The European Commission Framework 7 programme (EU FP7; HEALTH.2012.2.4.5-2, project number 305815; Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases). The Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115770, resources of which are composed of financial contribution from the European Union's Seventh Framework programme (FP7/2007-2013) and EFPIA companies' in-kind contribution. Details of the D-BOARD FP7 Consortium are available at: http://www.d-board.eu. Details of the APPROACH IMI Consortium are available at: https://www.approachproject.eu.
Copyright information: © 2019 Uzieliene, Bernotiene, Rakauskiene, Denkovskij, Bagdonas, Mackiewicz, Porvaneckas, Kvederas and Mobasheri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
  https://creativecommons.org/licenses/by/4.0/