Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere24876
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 12 2011

Fingerprint

Human Immunodeficiency Virus env Gene Products
osteoblasts
Osteoblasts
Human immunodeficiency virus
apoptosis
Apoptosis
proteins
Bone
Cells
CXCR4 Receptors
Human Immunodeficiency Virus Proteins
osteoporosis
bone density
HIV infections
Cell death
cells
G-proteins
GTP-Binding Proteins
Bone Density
Osteoporosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

@article{404cd0bb79d14e1aad1e1e4d334f023f,
title = "Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations",
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.",
author = "Cummins, {Nathan W} and Anna Klicpera and Sainski, {Amy M.} and Bren, {Gary D.} and Sundeep Khosla and Westendorf, {Jennifer J} and Badley, {Andrew David}",
year = "2011",
month = "9",
day = "12",
doi = "10.1371/journal.pone.0024876",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations

AU - Cummins, Nathan W

AU - Klicpera, Anna

AU - Sainski, Amy M.

AU - Bren, Gary D.

AU - Khosla, Sundeep

AU - Westendorf, Jennifer J

AU - Badley, Andrew David

PY - 2011/9/12

Y1 - 2011/9/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052641775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052641775&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0024876

DO - 10.1371/journal.pone.0024876

M3 - Article

C2 - 21931863

AN - SCOPUS:80052641775

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e24876

ER -