Downregulation of Gnas, Got2 and Snord32a following tenofovir exposure of primary osteoclasts

被引：31

作者：

Grigsby, Iwen F. ^{[1
,2
,3
,4
,5
]}

Pham, Lan ^{[1
,2
,4
]}

Gopalakrishnan, Raj ^{[3
,4
]}

Mansky, Louis M. ^{[3
,4
,5
]}

Mansky, Kim C. ^{[1
,2
,4
]}

机构：

[1] Univ Minnesota, Div Orthodont, Sch Dent, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Minneapolis, MN 55455 USA

[3] Univ Minnesota, Dept Diagnost & Biol Sci, Sch Dent, Minneapolis, MN 55455 USA

[4] Univ Minnesota, MinnCResT Program, Sch Dent, Minneapolis, MN 55455 USA

[5] Univ Minnesota, Acad Hlth Ctr, Inst Mol Virol, Minneapolis, MN 55455 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 391卷 / 03期

关键词：

HIV; HAART; Osteoblast; G-protein; AST; snoRNA; REVERSE-TRANSCRIPTASE INHIBITORS; SMALL NUCLEOLAR RNAS; HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MINERAL DENSITY; DISOPROXIL FUMARATE; MITOCHONDRIAL TOXICITY; CORTICAL BONE; NUCLEOSIDE; MOUSE; COMBINATION;

D O I：

10.1016/j.bbrc.2009.12.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Clinical observations have implicated the antiretroviral drug tenofovir with bone density loss during the management of HIV infection. The goal of this study was to investigate the in vitro effects of tenofovir exposure of primary osteoclasts in order to gain insights into the potential mechanisms for the drug-induced bone density loss. We hypothesized that tenofovir may alter the expression of key genes involved in osteoclast function. To test this, primary osteoclasts were exposed to physiologically relevant concentrations of the prodrug tenofovir disoproxil fumarate (TDF), then intensive microarray analysis was done to compare tenofovir-treated versus untreated cells. Specific downregulation of Gnas, Got2 and Snord32a were observed in the TDF-treated cells. The functions of these genes help to explain the basis for tenofovir-associated bone density loss. Our studies represent the first analysis of the effects of tenofovir on osteoclast gene expression and help to explain the basis of tenofovir-associated bone density loss in HIV-infected individuals. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：1324 / 1329

页数：6

共 29 条

[1] Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults [J].