Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

Gergely Becs, Abolfazl Zarjou, Anupam Agarwal, Katalin Éva Kovács, Ádám Becs, Mónika Nyitrai, Eniko Balogh, Emese Bányai, John W. Eaton, Paolo Arosio, Maura Poli, V. Jeney, J. Balla, G. Balla

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Abstract

Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3, or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification.

Original languageEnglish
Pages (from-to)217-230
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Volume20
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Ferritins
Smooth Muscle Myocytes
Cholecalciferol
Pharmacology
Vascular Calcification
Osteoblasts
Alkaline Phosphatase
Apoferritins
Tunica Media
Calcium
Glycerophosphates
Calcitriol
Osteocalcin
Diabetes Complications
Chronic Renal Insufficiency
Phosphorus
Extracellular Matrix
Renal Dialysis
Atherosclerosis
Phosphates

Keywords

  • Ferritin
  • Ferroxidase activity
  • Vascular calcification
  • Vitamin D
  • β-glycerophosphate

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells. / Becs, Gergely; Zarjou, Abolfazl; Agarwal, Anupam; Kovács, Katalin Éva; Becs, Ádám; Nyitrai, Mónika; Balogh, Eniko; Bányai, Emese; Eaton, John W.; Arosio, Paolo; Poli, Maura; Jeney, V.; Balla, J.; Balla, G.

In: Journal of Cellular and Molecular Medicine, Vol. 20, No. 2, 01.02.2016, p. 217-230.

Research output: Contribution to journalArticle

Becs, G, Zarjou, A, Agarwal, A, Kovács, KÉ, Becs, Á, Nyitrai, M, Balogh, E, Bányai, E, Eaton, JW, Arosio, P, Poli, M, Jeney, V, Balla, J & Balla, G 2016, 'Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells', Journal of Cellular and Molecular Medicine, vol. 20, no. 2, pp. 217-230. https://doi.org/10.1111/jcmm.12682
Becs, Gergely ; Zarjou, Abolfazl ; Agarwal, Anupam ; Kovács, Katalin Éva ; Becs, Ádám ; Nyitrai, Mónika ; Balogh, Eniko ; Bányai, Emese ; Eaton, John W. ; Arosio, Paolo ; Poli, Maura ; Jeney, V. ; Balla, J. ; Balla, G. / Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells. In: Journal of Cellular and Molecular Medicine. 2016 ; Vol. 20, No. 2. pp. 217-230.
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