Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

Carrillo-López, Natalia; Panizo, Sara; Arcidiacono, Maria Vittoria; de la Fuente, Sandra; Martínez-Arias, Laura; Ottaviano, Emerenziana; Ulloa, Catalina; Ruiz-Torres, María Piedad; Rodríguez, Isabel; Cannata-Andía, Jorge B.; Naves-Díaz, Manuel; Dusso, Adriana S.

doi:10.3390/nu14132589

Open AccessArticle

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

by

Natalia Carrillo-López

^1,2,†

,

Sara Panizo

^1,2,†,

Maria Vittoria Arcidiacono

^3,‡,

Sandra de la Fuente

^3,‡,

Laura Martínez-Arias

^1,2,

Emerenziana Ottaviano

¹,

Catalina Ulloa

¹,

María Piedad Ruiz-Torres

^2,4,

Isabel Rodríguez

¹

,

Jorge B. Cannata-Andía

^1,2,5,*,

Manuel Naves-Díaz

^1,2,§ and

Adriana S. Dusso

^1,3,6,*,§

¹

Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain

²

Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), 28040 Madrid, Spain

³

Division of Experimental Nephrology, IRB Lleida, 25198 Lleida, Spain

⁴

Departamento de Biología de Sistemas, Universidad de Alcalá, 28801 Alcalá de Henares, Spain

⁵

Departamento de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain

⁶

Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

^§

These authors contributed equally to this work.

Nutrients 2022, 14(13), 2589; https://doi.org/10.3390/nu14132589

Submission received: 26 May 2022 / Revised: 20 June 2022 / Accepted: 20 June 2022 / Published: 22 June 2022

(This article belongs to the Special Issue Vitamin D Receptor in Human Health and Disease)

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Abstract

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.

Keywords: vascular injury; osterix; α-actin; runx2; osteogenic differentiation; vitamin D

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MDPI and ACS Style

Carrillo-López, N.; Panizo, S.; Arcidiacono, M.V.; de la Fuente, S.; Martínez-Arias, L.; Ottaviano, E.; Ulloa, C.; Ruiz-Torres, M.P.; Rodríguez, I.; Cannata-Andía, J.B.; et al. Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia. Nutrients 2022, 14, 2589. https://doi.org/10.3390/nu14132589

AMA Style

Carrillo-López N, Panizo S, Arcidiacono MV, de la Fuente S, Martínez-Arias L, Ottaviano E, Ulloa C, Ruiz-Torres MP, Rodríguez I, Cannata-Andía JB, et al. Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia. Nutrients. 2022; 14(13):2589. https://doi.org/10.3390/nu14132589

Chicago/Turabian Style

Carrillo-López, Natalia, Sara Panizo, Maria Vittoria Arcidiacono, Sandra de la Fuente, Laura Martínez-Arias, Emerenziana Ottaviano, Catalina Ulloa, María Piedad Ruiz-Torres, Isabel Rodríguez, Jorge B. Cannata-Andía, and et al. 2022. "Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia" Nutrients 14, no. 13: 2589. https://doi.org/10.3390/nu14132589

APA Style

Carrillo-López, N., Panizo, S., Arcidiacono, M. V., de la Fuente, S., Martínez-Arias, L., Ottaviano, E., Ulloa, C., Ruiz-Torres, M. P., Rodríguez, I., Cannata-Andía, J. B., Naves-Díaz, M., & Dusso, A. S. (2022). Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia. Nutrients, 14(13), 2589. https://doi.org/10.3390/nu14132589

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Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

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