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.
authors.affiliation: Division of Infectious Disease, Mayo Clinic, Rochester, Minnesota, United States of America. Cummins.nathan@mayo.edu
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Cummins
authors.forename: Anna
authors.initials: A
authors.lastname: Klicpera
authors.forename: Amy M
authors.initials: AM
authors.lastname: Sainski
authors.forename: Gary D
authors.initials: GD
authors.lastname: Bren
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Badley
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; D019394:Ki-67 Antigen; D019718:Receptors, CXCR4