Inhibition of osteoblast differentiation by ritonavir

Wakabayashi,Yoshitaka; Yoshino,Yusuke; Seo,Kazunori; Koga,Ichiro; Kitazawa,Takatoshi; Ota,Yasuo

doi:10.3892/br.2018.1154

Inhibition of osteoblast differentiation by ritonavir

Authors:
- Yoshitaka Wakabayashi
- Yusuke Yoshino
- Kazunori Seo
- Ichiro Koga
- Takatoshi Kitazawa
- Yasuo Ota
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Affiliations: Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo 113‑8655, Japan, Department of Internal Medicine, Teikyo University, Tokyo 173‑8606, Japan
Published online on: October 2, 2018 https://doi.org/10.3892/br.2018.1154
Pages: 491-496
Copyright: © Wakabayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoporosis is one of the chronic complications seen in human immunodeficiency virus (HIV)‑infected patients, and affects patients at high prevalence. The causes of osteoporosis in HIV‑infected patients are multiple, and include chronic HIV infection, living habits such as smoking and alcohol consumption, and antiretroviral drug use. Among antiretroviral drugs, protease inhibitors have been reported to be associated with osteoporosis. However, it remains to be determined how anti‑HIV drugs affect osteoblast differentiation. In the current study, MC3T3‑E1 cells, a mouse osteoblastic cell line, were cultured in osteoblast differentiation medium with or without different protease inhibitors (ritonavir, lopinavir, darunavir or atazanavir), and alkaline phosphatase (ALP) activity and the expression of Runt‑related transcription factor 2 (Runx2) were analyzed. The ALP activity in MC3T3‑E1 cells cultured with ritonavir was significantly reduced compared with that in cells in only osteoblast inducer reagent, indicating that ritonavir inhibited osteoblast differentiation. Meanwhile, ALP activity was not reduced in cells cultured with any of the other inhibitors. In addition, ritonavir inhibited the expression of Runx2, a key regulator of osteoblast differentiation, in the early period of osteoblast differentiation. To the best of our knowledge, this is the first study to demonstrate that ritonavir inhibits osteoblast differentiation in vitro. The present findings may explain the mechanism of osteopenia induced by combination antiretroviral therapy involving protease inhibitors.

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