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Inhibition of osteoblast differentiation by ritonavir

Yoshitaka Wakabayashi1, Yusuke Yoshino2, Kazunori Seo2

  • 1Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo 113-8655, Japan.

Biomedical Reports
|December 15, 2018
PubMed

Insights

Ritonavir, an anti-HIV protease inhibitor, was found to inhibit osteoblast differentiation in vitro. This finding may explain the link between protease inhibitor use and osteoporosis in HIV patients.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Pharmacology

Background:

  • Osteoporosis is a common complication in patients with human immunodeficiency virus (HIV).
  • Antiretroviral drugs, particularly protease inhibitors, are suspected contributors to osteoporosis in HIV-infected individuals.
  • The precise mechanisms by which anti-HIV drugs impact bone health remain incompletely understood.

Purpose of the Study:

  • To investigate the effect of specific protease inhibitors on osteoblast differentiation in vitro.
  • To determine if ritonavir, lopinavir, darunavir, or atazanavir inhibit the differentiation of osteoblastic cells.

Main Methods:

  • MC3T3-E1 cells, a mouse osteoblastic cell line, were cultured in differentiation medium.
  • Cells were treated with or without various protease inhibitors (ritonavir, lopinavir, darunavir, atazanavir).
  • Alkaline phosphatase (ALP) activity and Runt-related transcription factor 2 (Runx2) expression were analyzed.

Main Results:

  • Ritonavir significantly reduced ALP activity, indicating inhibition of osteoblast differentiation.
  • No significant reduction in ALP activity was observed with lopinavir, darunavir, or atazanavir.
  • Ritonavir also inhibited the early expression of Runx2, a critical transcription factor for osteoblast differentiation.

Conclusions:

  • Ritonavir inhibits osteoblast differentiation in vitro, suggesting a potential mechanism for osteoporosis development in HIV patients on protease inhibitor therapy.
  • This study provides the first in vitro evidence of ritonavir's inhibitory effect on osteoblast differentiation.
  • Findings may elucidate the role of protease inhibitors in antiretroviral therapy-induced osteopenia.

Keywords:
antiretroviral therapyhuman immunodeficiency virusosteoblast differentiationosteoporosisprotease inhibitorritonavir

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