Division of Orthodontics, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):48-53. doi: 10.1016/j.bbrc.2010.02.080. Epub 2010 Feb 18.
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.
有强有力的临床证据表明，替诺福韦在治疗人类免疫缺陷病毒感染时会导致骨密度降低。在这项研究中，我们试图验证一个假设，即替诺福韦处理成骨细胞会导致基因表达谱的变化，从而影响骨形成过程中成骨细胞的功能。我们分离了原代成骨细胞，然后用替诺福韦前药替诺福韦二吡呋酯（TDF）处理。从 TDF 处理和未处理的成骨细胞中提取总 RNA，并用于微阵列分析，以评估 TDF 相关的基因表达谱变化。引人注目的是，细胞信号转导、细胞周期和氨基酸代谢相关的基因表达谱变化，这可能会影响成骨细胞在骨形成中的功能。我们的研究结果首次表明，替诺福韦处理原代成骨细胞会导致基因表达变化，这暗示了替诺福韦相关的骨密度降低与成骨细胞功能丧失有关。
