Suppressive effects of tenofovir disoproxil fumarate, an antiretroviral prodrug, on mineralization and type II and type III sodium-dependent phosphate transporters expression in primary human osteoblasts

Anna Maria Barbieri, Iacopo Chiodini, Enrico Ragni, Graziana Colaianni, Franco Gadda, Marco Locatelli, Pietro Lampertico, Anna Spada, Cristina Eller-Vainicher

Research output: Contribution to journalArticlepeer-review

Abstract

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug commonly used for the management of Human Immunodeficiency Virus (HIV) in highly active antiretroviral therapy (HAART) and of chronic Hepatitis B Virus (HBV) infections. Long-term TDF-treated subjects present decrease of bone mineral density and rarely severe osteomalacia. Although these adverse effects have been attributed to the impaired proximal tubule function, a possible direct involvement of TDF on osteoblasts should be taken into account. The aim of this study was to evaluate whether sodium phosphate transporters NPT2A (sodium-dependent phosphate transport protein 2A), NPT2C (sodium-dependent phosphate transport protein 2C), PIT1 (sodium-dependent phosphate transporter 1), and PIT2 (sodium-dependent phosphate transporter 2) were expressed in primary human osteoblasts (HOBs), whether their expression was related to HOBs differentiation and whether TDF could affect mineralization and gene expression. PIT1 and PIT2 were expressed under proliferating conditions and increased after induction of mineralization, while NPT2A and NPT2C were almost undetectable. In HOBs TDF exposure induced a significant dose-dependent decrease in mineralization. Moreover, TDF caused a reduction of COL1A1 and of ATF4 expression in differentiated HOBs. In summary, HOBs do not express NPT2A and NPT2C and do express PIT1 and PIT2, suggesting a role of these two latter in human osteoblast mineralization. TDF impairs osteoblast mineralization, confirming a direct negative effect on bone. Therefore, in clinical practice, bone damage must be suspected and evaluated also in patients receiving TDF without kidney function alterations.

Original languageEnglish
Pages (from-to)4855-4866
JournalJournal of Cellular Biochemistry
Volume119
Issue number6
DOIs
Publication statusPublished - 2018

Keywords

  • Bone
  • HIV
  • Mineralization
  • Osteoblasts
  • Sodium phosphate transporters
  • Tenofovir

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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