Abstract
Aging is associated with the development of various chronic diseases, in which both hypertension and osteoarthritis (OA) are dominant. Currently, there is no effective treatment for OA, whereas hypertension is often treated using L-type voltage-operated calcium channel (VOCC) blocking drugs, nifedipine being among the most classical ones. Although nifedipine together with other VOCC inhibitors plays an important role in people wellbeing, there are unresolved questions on its possible effect on cartilage tissue homeostasis and the development of OA. Due to that, the aim of this study was to analyse the effects of nifedipine on metabolic processes in human chondrocytes and bone marrow mesenchymal stem cells (BMMSCs). To analyze whether those events were mediated specifically through VOCC, agonist BayK8644 was used. Our results demonstrate that nifedipine downregulated chondrocyte proliferation rate as well as mitochondrial respiration and ATP production (Agilent Seahorse) in both cell types. Analysis of cartilage explant histological sections by electron microscopy also suggested that part of mitochondria lose their activity in response to nifedipine.However, switch of energetic metabolic pathway towards glycolytic was observed only in chondrocytes. Stimulation with either nifedipine or BayK8644 resulted in elevated production of collagen type II and proteoglycans in micromass cultures under chondrogenic condition, although the effects of VOCC inhibitor Bay8466 were less expressed. Nitric oxide (NO) activity, as measured by flow cytometry, was upregulated by nifedipine in BMMSCs and particularly chondrocytes, suggesting that NO at least in part may account for the effects of nifedipine on metabolism in both tested cell types.Taken together, we conclude that antihypertensive drug nifedipine inhibits mitochondrial respiration in both chondrocytes and BMMSCs and that these effects may be associated with increased NO accumulation and pro-inflammatory activity. Glycolytic capacity was enhanced only in chondrocytes, suggesting that these cells have the capacity to switch from oxidative phosphorylation to glycolysis and alter their metabolic activity in response to VOCC inhibition. Finally, nifedipine stimulated production of collagen type II and proteoglycans in both cell types, implying its potentially beneficial anabolic effects on articular cartilage. These results highlight a potential link between consumption of antihypertensive drugs and cartilage health
Activin and Nodal Are Not Suitable Alternatives to TGFβ for Chondrogenic Differentiation of Mesenchymal Stem Cells
