Division of Infectious Disease, Mayo Clinic, Rochester, Minnesota, United States of America.
PLoS One. 2011;6(9):e24876. doi: 10.1371/journal.pone.0024876. Epub 2011 Sep 12.
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.
与未感染的患者相比，HIV 感染者的成骨细胞数量减少、骨密度降低、骨折风险增加；然而，这些关联的分子机制仍不清楚。我们质疑 HIV 包膜蛋白的组成部分 Gp120 是否能够诱导许多细胞类型的凋亡，是否能够诱导成骨细胞（形成骨骼的细胞）死亡。我们发现，在体外生理浓度下用外源性 Gp120 处理永生化成骨样细胞和原代人成骨细胞不会导致细胞凋亡。相反，在成骨样 U2OS 细胞系中，与对照组相比，表达 Gp120 受体 CXCR4 的细胞在 Gp120 处理后增殖增加（P<0.05），用 CXCR4 抑制剂和 G 蛋白抑制剂预处理可抑制这种增殖。这表明 Gp120 不是人成骨细胞凋亡的诱导剂，并且可能不会通过这种机制直接导致感染患者的骨质疏松症。
