Department of Haematology and Oncological Sciences, Microbiology Section, University of Bologna, Italy.
Biochem Biophys Res Commun. 2010 Oct 22;401(3):429-34. doi: 10.1016/j.bbrc.2010.09.071. Epub 2010 Sep 24.
Impaired osteoblast/osteoclast cross-talk and bone structure homeostasis resulting in osteopenia/osteoporosis are often observed in HIV seropositive patients but the causal mechanisms remain unsettled. This study analyzed the biological effects of Tat on peripheral blood monocyte-derived osteoclast differentiation. Tat enhances osteoclast differentiation and activity induced by RANKL plus M-CSF treatment increasing both the mRNA expression of specific osteoclast differentiation markers, such as cathepsin K and calcitonin receptor, and TRAP expression and activity. These Tat-related biological effects may be related, at least in part, to the induction of c-fos expression and AP-1 activity. c-fos up-regulation was triggered by Tat when cell cultures were co-treated with RANKL/M-CSF and an analysis of c-fos promoter with c-fos deletion mutant constructs disclosed specific c-fos promoter domains targeted by Tat. Together, these results show that Tat may be considered a viral factor positively modulating the osteoclastogenesis and then bone resorption activity suggesting a pathogenetic role of this viral protein in the HIV-related osteopenia/osteoporosis.
艾滋病毒血清阳性患者常出现破骨细胞/成骨细胞交叉对话受损和骨结构失衡，导致骨质疏松/骨量减少，但因果机制尚不清楚。本研究分析了 Tat 对外周血单核细胞来源的破骨细胞分化的生物学影响。Tat 增强了 RANKL 加 M-CSF 处理诱导的破骨细胞分化和活性，增加了特定的破骨细胞分化标志物，如组织蛋白酶 K 和降钙素受体的 mRNA 表达以及 TRAP 的表达和活性。这些与 Tat 相关的生物学效应至少部分与 c-fos 表达和 AP-1 活性的诱导有关。当细胞培养物与 RANKL/M-CSF 共同处理时，Tat 触发了 c-fos 的上调，并且对 c-fos 启动子与 c-fos 缺失突变构建体的分析揭示了 Tat 靶向的特定 c-fos 启动子区域。总之，这些结果表明，Tat 可被视为一种正向调节破骨细胞生成和随后的骨吸收活性的病毒因子，提示这种病毒蛋白在 HIV 相关骨质疏松/骨量减少中具有致病作用。
