Tenofovir treatment of primary osteoblasts alters gene expression profiles: implications for bone mineral density loss.
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.
Grigsby
Iwen F
IF
Division of Orthodontics, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Pham
Lan
L
Mansky
Louis M
LM
Gopalakrishnan
Raj
R
Carlson
Ann E
AE
Mansky
Kim C
KC
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects* / Q000235:genetics; D001862:Bone Resorption / Q000139:chemically induced* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D063065:Organophosphonates / Q000009:adverse effects* / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011355:Prodrugs / Q000009:adverse effects / Q000494:pharmacology; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D011355:Prodrugs; D000068698:Tenofovir; D000225:Adenine