HIV-1 Tat protein enhances RANKL/M-CSF-mediated osteoclast differentiation
HIV-1 Tat protein enhances RANKL/M-CSF-mediated osteoclast differentiation
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DOI：
10.1016/j.bbrc.2010.09.071
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发表时间：
2010-10-22
影响因子：
3.1
通讯作者：
Re, Maria Carla
中科院分区：
文献类型：
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作者：
Gibellini, Davide;De Crignis, Elisa;Re, Maria Carla
在HIV血清阳性患者中经常观察到成骨细胞/破骨细胞相互作用和骨结构稳态受损导致骨质减少/骨质疏松，但其因果机制尚不清楚。本研究分析了Tat对外周血单核细胞源性破骨细胞分化的生物学作用。RANKL + M-CSF诱导的破骨细胞分化和活性增强，使组织蛋白酶K和降钙素受体等特定破骨细胞分化标志物mRNA表达和TRAP表达和活性增加。这些与tat相关的生物学效应可能至少部分与c-fos表达和AP-1活性的诱导有关。当细胞培养物与RANKL/M-CSF共处理时，Tat触发c-fos上调，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启动子结构域。总之，这些结果表明，Tat可能被认为是一种积极调节破骨细胞发生和骨吸收活性的病毒因子，这表明该病毒蛋白在hiv相关的骨质减少/骨质疏松症中起着致病作用。(C) 2010爱思唯尔公司版权所有。
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. (C) 2010 Elsevier Inc. All rights reserved.