Human Immunodeficiency Virus Envelope Protein Gp120 Induces Proliferation but Not Apoptosis in Osteoblasts at Physiologic Concentrations

Nathan W Cummins,Andrew D Badley,Anna Klicpera,Amy M Sainski,Sundeep Khosla,Jennifer J Westendorf,Gary D Bren,Clive M Gray

doi:10.1371/journal.pone.0024876

Nathan W Cummins, Andrew D Badley + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0024876

Copy DOI

Journal: PLoS ONE	Publication Date: Sep 12, 2011
Citations: 8	License type: CC BY 4.0

Affiliation: Mayo Clinic, Winneshiek Medical Center

Abstract

Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05), which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism.

Highlights

Prior to the advent of highly active antiretroviral therapy (HAART), HIV infection was considered to be fatal
Because the number of osteoblasts is decreased in HIV-infected patients, and Gp120 has been shown to have pro-apoptotic effects on multiple cell types, we first sought to determine whether Gp120 induces apoptosis in human immortalized fetal osteoblasts
These results indicate that Gp120 itself does not induce apoptotic cell death in these osteoblasts tested

Summary

Introduction

Prior to the advent of highly active antiretroviral therapy (HAART), HIV infection was considered to be fatal. Administration of HAART, in resource-rich settings, has dramatically changed the clinical course of the disease, with patients newly infected with HIV expected to have a near normal life expectancy. HIV-infected patients have lower bone mineral density, and higher prevalences of both osteopenia and osteoporosis, compared to age and sex matched HIVuninfected controls [2,3,4]. This translates into an increased risk of fracture and decreased rate of fracture healing [5,6]. The cause of the increased bone disease seen in HIV infection, remains unclear

Methods

Results

Conclusion