HIV-1 replicates in human osteoclasts and enhances their differentiation in vitro.

Jin Gohda,Ying Huang,Jun-Ichiro Inoue,Takaomi Ishida,Yijing Ma,Lijun Gu,Aikichi Iwamoto,George Fu Gao,Yang Han,Bin Gao,Taisheng Li,Yu Zhang

doi:10.1186/s12977-015-0139-7

Abstract

BackgroundHIV-1 infected patients frequently have osteolytic bone disease, which is caused by the dysregulation of the bone remodeling system that involves the interaction between osteoblasts and osteoclasts, but the relationship between osteolytic disease and HIV-1 infection remains unclear. In this study we tested whether HIV-1 infection of osteoclasts affects their differentiation.ResultsWe prepared human osteoclasts from CD14+ monocytes and examined them for their susceptibility to HIV-1. Furthermore, we investigated the effect of HIV-1 infection on osteoclast differentiation. CD14-derived osteoclasts were shown to express CD4, CCR5, and CXCR4 each at the similar level to that shown with macrophages. R5-tropic HIV-1 and X4-tropic HIV-1 were found to infect CD14-derived osteoclasts and replicate in them. Furthermore, HIV-1 infection induced formation of larger osteoclastst, enhanced the expression of mRNAs for three osteoclast specific marker molecules (tartrate-resistant acid phosphatase, cathepsin K, and the calcitonin receptor), and up-regulated osteoclast bone resorption activity.ConclusionsOur results suggest that osteoclasts serve as a novel target for HIV-1 infection, which may enhance the osteoclast differentiation contributing to the development of osteolytic disease in HIV-1-infected patients.

Highlights

HIV-1 infected patients frequently have osteolytic bone disease, which is caused by the dysregulation of the bone remodeling system that involves the interaction between osteoblasts and osteoclasts, but the relationship between osteolytic disease and HIV-1 infection remains unclear
Our results suggest that osteoclasts serve as a novel target for HIV-1 infection, which may enhance the osteoclast differentiation contributing to the development of osteolytic disease in HIV-1-infected patients
CD14-derived osteoclasts are susceptible to HIV infection in vitro We characterized human osteoclasts generated by culturing with recombinant macrophage colony-stimulating factor (M-CSF) plus RANKL the CD14+ monocytes purified from peripheral blood mononuclear cells (PBMCs) [9]

Summary

Introduction

HIV-1 infected patients frequently have osteolytic bone disease, which is caused by the dysregulation of the bone remodeling system that involves the interaction between osteoblasts and osteoclasts, but the relationship between osteolytic disease and HIV-1 infection remains unclear. We investigated the effect of HIV-1 infection on osteoclast differentiation. HIV-1 infection induced formation of larger osteoclastst, enhanced the expression of mRNAs for three osteoclast specific marker molecules (tartrate-resistant acid phosphatase, cathepsin K, and the calcitonin receptor), and up-regulated osteoclast bone resorption activity. The increased average life span has given rise to long-term complications of HIV-1 infection, resulting in cardiovascular disease, hepatic toxicity, and metabolic disorder [1,2]. Osteolytic bone disease has emerged as one of these complications Osteolytic bone disease, such as osteoporosis or osteopenia, is characterized by reduction of bone mineral density (BMD). One meta-analysis of prevalence data on osteolytic disease demonstrated that BMD reduction was observed in 67% of HIV-1-infected patients [3].

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