Effects of Antiretroviral Molecules on Survival and Gene Expression of An Osteoblast-like Cell Line

Author(s): Anna Miserocchi, Giuseppina Musumeci, Isabella Bon, Silvia Morini, Serena Longo, Marco Borderi, Davide Gibellini, Maria Carla Re*.

Journal Name: Current HIV Research

Volume 14 , Issue 6 , 2016

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Abstract:

Background: The advent of combined antiretroviral therapy effectively undermined the evolution of HIV disease. Nevertheless, clinical observations indicated a clear association between therapy and the impairment of bone mineral density.

Objective: We selected some antiretroviral compounds used in clinical practice, to study their impact on bone health and their possible implication in the onset of bone disease.

Method: Scalar concentrations of several antiretroviral drugs (used in single and in combination) were tested on an osteoblast-like cell line, HOBIT cells, to analyse cell survival and gene expression of selected bone markers.

Results: None of the tested concentrations of Tenofovir, Emtricitabine, Nevirapine, Maraviroc or Raltegravir induced any significant apoptosis activation at our experimental conditions. Only some protease inhibitors and Efavirenz, at high concentration, determined a significant activation of programmed cell death. In parallel experiments, protease inhibitors used in combination with Tenofovir and Emtricitabine, increased apoptosis. Furthermore, we performed a study of mRNA expression of specific genes involved in osteoblast biology and in bone synthesis and observed that some protease inhibitors induced a selective decrease of some osteogenic markers.

Conclusion: All the protease inhibitors included in this study trigger apoptosis at the highest concentration analysed, suggesting great caution in HIV-patients co-infected with HBV or HCV, where elevated plasma concentrations of drugs could be reached as a consequence of liver failure. Lastly, an increased apoptosis rate and an impairment of osteogenic markers were recorded only in the presence of Nelfinavir, suggesting a role of protease inhibitors in the alteration of osteoblast biology.

Keywords: Antiretroviral therapy, apoptosis, bone, co-morbidity, gene expression, HIV, osteoblasts,

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Article Details

VOLUME: 14
ISSUE: 6
Year: 2016
Page: [497 - 505]
Pages: 9
DOI: 10.2174/1570162X14666160518121915
Price: $58

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