Tenofovir treatment of primary osteoblasts alters gene expression profiles: Implications for bone mineral density loss

Iwen F. Grigsby, Lan Pham, Louis M. Mansky, Raj Gopalakrishnan, Ann E. Carlson, Kim C. Mansky

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

There is strong clinical evidence that implicates tenofovir in the loss of bone mineral density during treatment of human immunodeficiency virus infection. In this study, we sought to test the hypothesis that tenofovir treatment of osteoblasts causes changes in the gene expression profile that would impact osteoblast function during bone formation. Primary osteoblasts were isolated and then treated with the tenofovir prodrug, tenofovir disoproxil fumarate (TDF). Total RNA from TDF-treated and untreated osteoblasts were extracted and used for microarray analysis to assess TDF-associated changes in the gene expression profile. Strikingly, the changes in gene expression profiles involved in cell signaling, cell cycle and amino acid metabolism, which would likely impact osteoblast function in bone formation. Our findings demonstrate for the first time that tenofovir treatment of primary osteoblasts results in gene expression changes that implicate loss of osteoblast function in tenofovir-associated bone mineral density loss.

Original languageEnglish (US)
Pages (from-to)48-53
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume394
Issue number1
DOIs
StatePublished - Mar 26 2010

Bibliographical note

Funding Information:
The following reagent was obtained through the NIH AIDS Research and Reference Reagent program, Division of AIDS, NIAID, NIH: Tenofovir disoproxil fumarate, Catalog Number 10198. We thank Andy Kaplan for stimulating discussions, and David Largaespada and Raha Allaei for assistance with mice. Supported by NIH grants AR53946 (to K.C.M.), DE16093 (to R.G.), and GM56615 (to L.M.M.). I.F.G. and L.P. were supported by T32DE07288.

Keywords

  • Bone
  • Cell cycle
  • HIV
  • Metabolism
  • Nucleotide
  • Osteoclast
  • Signaling

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